Manuela Mengozzi - Profile on Academia.edu (original) (raw)

Papers by Manuela Mengozzi

bioRxiv (Cold Spring Harbor Laboratory), Aug 9, 2019

Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but there is uncert... more Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but there is uncertainty about what dose and form of vitamin D could improve the clinical course of MS. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with D3 at 24 h and 72 h following onset of differentiation. Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1,272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for gene ontology categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. These findings should help to identify mechanisms mediating D3 action in MS.

Tumor Necrosis Factor-Α Drives HIV-1 Replication in U937 Cell Clones and Upregulates CXCR4

Cytokine, 2001

U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been ... more U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been described. We evaluated the role of host factors in their differential ability to support HIV-1 replication. Plus clones constitutively produced TNF-alpha and viral replication was inhibited by neutralization of endogenous TNF-alpha. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-alpha, which also further accelerated the kinetics of infection in plus clones. We observed an increased accumulation of proviral DNA within one round of HIV-1 replication following TNF-a treatment of plus cells. This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identify TNF-alpha as one correlate that contributes to the higher ability of U937-plus clones to sustain HIV-1 replication. Furthermore, we suggest that TNF-alpha may affect steps of the viral life cycle that occur earlier than transcription and also enhance HIV-1 replication by increasing the surface density of CXCR4.

Blood, Mar 15, 1999

We have recently described a significant correlation between human immunodeficiency virus-1 (HIV-... more We have recently described a significant correlation between human immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the acquired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because local macrophages (microglia) are the cells predominantly infected in the brain, we investigated whether in vitro HIV infection affects MCP-1 production in mononuclear phagocytes (MP). MCP-1 secretion and expression were consinstently upregulated over constitutive levels in human monocyte-derived macrophages (MDM) infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was required for this effect, as demonstrated by the absence of chemokine upregulation after infection in the presence of 3'-azido-3'-deoxythimidine (AZT) or cell-exposure to heatinactivated (⌬°) virus. MCP-1 induction was not restricted to HIV-1 BaL, but was also observed during productive infection of MDM with two primary isolates differing for entry coreceptor usage and of U937 cells with the X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1 Tat induced MCP-1 expression in astrocytes, we also investigated its role in MDM and U937 cells. Exogenous Tat induced MCP-1 production from MDM in a concentration-dependent manner, however, it was not effective on uninfected U937 cells or on the chronically infected U937-derived cell line U1. Transfection of Tat-expressing plasmids moderately activated HIV expression in U1 cells, but failed to induce MCP-1 expression in this cell line or in uninfected U937 cells. HIV replicationdependent expression of MCP-1 in MP may be of particular relevance for the pathogenesis of HIV infection in nonlymphoid organs such as the brain.

グルタチオンはその抗酸化特性と独立してマクロファージ細胞株における抗ウイルス経路に対する自然免疫応答を調整する【JST・京大機械翻訳】

Frontiers in Immunology (Web), 2017

Proceedings of the National Academy of Sciences of the United States of America, Jul 25, 2000

Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells

European Journal of Immunology, Feb 1, 1993

After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin... more After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)‐1, now re‐named IL‐1 receptor antagonist (IL‐1ra). In this study we have examined the production of IL‐1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL‐1ra transcripts, which were considerably augmented after treatment with lipopolysaccharrides (LPS) and cytokines [IL‐4, granulocyte (G)‐and granulocyte macrophage (GM)‐Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL‐1 ra transcripts were comparable to those observed in endotoxin‐stimulated human monocytes. By contrast IL‐1β interferon (IFN)‐γ and chemotactic factors (fMLP, C5a and IL‐8) failed to promote IL‐1ra expression in PMN. IL‐1ra induction by LPS reached peak levels at 10 ng/ml after 3‐6 h and remained sustained 24 h after stimulation. Induction by LPS and GM‐CSF appears to be at the transcriptional level, as assessed by inhibiting mRN A synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL‐1ra mRNA. In addition to expressing mRNA, PMN also produce IL‐1ra protein. Secretion of IL‐1ra was induced in PMN treated with LPS, IL‐4 and GM‐CSF, but not by IL‐1β IFN‐γ and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL‐1ra, suggesting that PMN, while exerting a series of pro‐inflammatory activities, may also modulate the inflammatory potential of IL‐1 in tissues.

Journal of Virology, Nov 1, 2002

Immature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), r... more Immature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), responsible for primary antiviral immunity. IPC express surface molecules CD4, CCR5, and CXCR4, which are known coreceptors required for human immunodeficiency virus (HIV) infection. Here we show that IPC are susceptible to and replicate HIV type 1 (HIV-1). Importantly, viral replication is triggered upon activation of IPC with CD40 ligand, a signal physiologically delivered by CD4 T cells. Immunohistochemical staining of tonsil from HIV-infected individuals reveals HIV p24 ؉ IPC, consistent with in vivo infection of these cells. IPC exposed in vitro to HIV produce alpha interferon, which partially inhibits viral replication. Nevertheless, IPC efficiently transmit HIV-1 to CD4 T-cells, and such transmission is also augmented by CD40 ligand activation. IPC produce RANTES/CCL5 and MIP-1␣/CCL3 when exposed to HIV in vitro. IPC also induce naïve CD4 T cells to proliferate and would therefore preferentially infect these cells. These results indicate that IPC may play an important role in the dissemination of HIV.

CHEMOKINES Human Immunodeficiency Virus Replication Induces Monocyte Chemotactic

Serum Amyloid a Induction in Tumor-Bearing Mice-Evidence for a Tumor-Derived Mediator

Proceedings of the National Academy of Sciences of the United States of America, Sep 18, 2001

Stimulation with antibodies to CD3 and CD28 coimmobilized on beads can be used to significantly e... more Stimulation with antibodies to CD3 and CD28 coimmobilized on beads can be used to significantly expand T cells ex vivo. With CD4 T cells from HIV-infected patients, this expansion usually is accompanied by complete suppression of viral replication, presumed to be caused by down-regulation of the viral coreceptor CCR5 and up-regulation of CCR5 ligands. Here we show that this suppression occurs in total CD4 T cells acutely infected with R5 HIV, but not in purified CD62L ؊ memory CD4 T cells. The lack of complete suppression in these memory cells, typically comprising 10 -40% of total CD4 T cells, occurs despite high levels of CCR5 ligand secretion and down-regulation of CCR5. Significantly, adding back naı ¨ve or CD62L ؉ memory CD4 T cells inhibits the viral replication in the CD62L ؊ cells, with the naı ¨ve cells capable of completely repressing the virus. Although this inhibition was previously thought to be specific to bead-bound anti-CD3͞CD28 stimulation, we show that the same suppression is obtained with sufficiently strong anti-CD3͞B7.1 stimulation. Our results show that inhibitory mechanisms, expressed predominantly by strongly stimulated naı ¨ve CD4 T cells and mediated independently of CCR5-binding chemokines, play a role in the inhibition of R5 HIV replication in CD4 T cells upon CD28 costimulation. R esting CD4 T cells can be infected with HIV, but productive HIV infection requires T cell activation (1). Compared with stimulation via the T cell receptor-CD3 complex (2), the interaction of CD28 on the surface of CD4 ϩ T cells with its ligands CD80 (B7.1) and CD86 (B7.2) or with anti-CD28 antibodies (Abs) increases HIV replication in peripheral blood mononuclear cells (PBMC) (3, 4). Consistent with these findings, immune activation in vivo increases HIV replication (5). In contrast to these observations, Levine et al. (6) reported that stimulation of CD4 T cells of HIV-infected patients with anti-CD3 and anti-CD28 coimmobilized on Sepharose beads ''clears'' HIV from infected cultures, allowing ex vivo expansion of autologous CD4 T cells in the absence of antiretroviral drugs. The same authors later reported that this mode of stimulation decreases expression of the main HIV coreceptor CCR5 (7) and induces high levels of the HIV-inhibitory CCR5 ligands RANTES, macrophage inflammatory protein (MIP)-1␣, and MIP-1␤ (hereafter, CCR5 ligands) (8), that block access to CCR5, resulting in inhibition of CCR5-dependent (R5), but not of CXCR4-dependent (X4), HIV replication. Therefore, anti-CD3͞CD28 stimulation can result in decreased or enhanced HIV replication, apparently depending on the mode of stimulation [i.e., soluble Abs vs. Abs immobilized on beads ]. The differential effects of these modes of stimulation on CCR5 expression and CCR5 ligand secretion do not appear to resolve the controversy. Creson et al. (9) reported that continuous passage of CD4 T cells on plastic culture dishes coated with anti-CD3͞CD28 Abs failed to inhibit R5 HIV infection, despite decreased expression of CCR5 and secretion of CCR5 ligands at levels comparable to those achieved by stimulation with anti-CD3͞CD28 mAb-conjugated beads. Our findings indicate that the resolution of this paradox lies in the strength of T cell stimulation and in the heterogeneity of CD4 T cells. CD4 T cells can be divided into naı ¨ve T cells that express both CD45RA and CD62L and memory T cells . Memory cells can be further divided into a number of subsets, including M1 (CD45RA Ϫ CD62L Ϫ ) and M2 (CD45RA Ϫ CD62L ϩ ). We and others (12-15) have shown that naı ¨ve T cells support productive X4 HIV infection much less efficiently than memory T cells after CD3͞CD28 stimulation. In this article, we show that, as for X4 viruses, CD28costimulated naı ¨ve T cells do not support productive R5 HIV infection. We demonstrate that, in contrast to the suppression of R5 HIV replication in total CD4 stimulated by anti-CD3͞CD28 antibody-conjugated beads (6), R5 HIV can replicate at high levels in M1 cells stimulated with anti-CD3͞CD28 beads, despite down-regulation of CCR5 and secretion of high levels of CCR5 ligands. Furthermore, addition of purified naı ¨ve CD4 T cells to M1 cells reproduces the inhibition of HIV replication observed in total CD4 T cell cultures. Finally, inhibition of R5 HIV replication in CD4 T cells, but not in purified M1 cells, can be obtained with the more physiologically relevant anti-CD3͞B7.1 stimulation, by increasing the strength of the stimulus, under conditions that induce minimal levels of CCR5 ligands. Taken together, these results suggest that the strength of stimulation is critical for inhibition of R5 HIV replication and that mechanisms independent of CCR5 ligands, expressed by naı ¨ve CD4 T cells, are involved in this inhibition. Thus, we have identified a mechanism for the inhibition of R5 viruses that is a cross-regulatory phenomenon between subsets of CD4 T cells. Cell Culture Conditions. Cells were cultured at 37°C, 5% CO 2 in RPMI 1640 (GIBCO͞BRL) supplemented with 2 mM Lglutamine, 100 units͞ml penicillin, 50 nM streptomycin (GIBCO͞BRL), 20 mM Hepes (Sigma), 10% FBS (Atlanta Biologicals, Norcross, GA), and human recombinant IL-2 (50 units͞ml, from Maurice Gately, Hoffmann-La Roche, obtained through the AIDS Research and Reference Reagent Program,

Reversal of defective IL-6 production in lipopolysaccharide-tolerant mice by phorbol myristate acetate

Journal of Immunology, Aug 1, 1991

The development of LPS tolerance has been suggested to be mediated by an inhibition of cytokine s... more The development of LPS tolerance has been suggested to be mediated by an inhibition of cytokine synthesis. Here we have studied serum IL-6 and TNF levels in mice after LPS administration. Repeated administration of LPS (35 micrograms daily for 4 days) to mice induced a refractoriness (tolerance) to subsequent administrations of LPS in terms of induction of circulating IL-6 and TNF. To investigate the mechanism by which LPS down-regulates its own induction of cytokine synthesis and the relationship between IL-6 and TNF production, we attempted to revert the inhibition of IL-6 and TNF production using agents like PMA or IFN-gamma, previously reported to activate macrophage production of cytokines. Pretreatment with PMA (4 micrograms, 10 min before LPS) partially restored IL-6 production in LPS-tolerant mice given 2 micrograms LPS. On the other hand, PMA did not restore TNF induction in LPS-tolerant mice, even when administered with high doses of LPS (up to 200 micrograms). A similar reversal of LPS resistance to IL-6, but not TNF, induction by PMA was observed in genetically LPS-resistant C3H/HeJ mice. IFN-gamma also restored, although to a lesser extent than PMA, IL-6 production. However, unlike PMA, IFN-gamma could also partially restore TNF production in LPS-tolerant mice, although only when LPS was administered at high doses. By contrast with PMA, IFN-gamma was clearly more active in restoring TNF synthesis than that of IL-6. Similar results were obtained in genetically LPS-unresponsive C3H/HeJ mice. These data suggest that different mechanisms are implicated in the inhibition of IL-6 and TNF synthesis in LPS-tolerant mice and that part of this inhibition can be overcome by PMA or IFN-gamma.

Proteins identified from BioGEE-treated samples

PLOS ONE, May 18, 2015

<p>Proteins identified from BioGEE-treated samples.</p

International Journal of Immunopharmacology, 1991

Interleukin (IL-I) and tumor necrosis factor (TNF) are thought to play a key role in septic shock... more Interleukin (IL-I) and tumor necrosis factor (TNF) are thought to play a key role in septic shock and inflammation. We had previously shown that chlorpromazine (CPZ) has a protective effect in various models of endotoxic shock and IL-I toxicity. We have tested the effect of CPZ on several activities of IL-I in vivo. CPZ (4 mg/kg) inhibited increases in serum corticosterone, triglycerides and serum amyloid A (SAA). Chlorpromazine also antagonized these same effects when they were induced by endotoxin or TNF, suggesting that this activity could be implicated in the protective effect of CPZ in various models of endotoxic shock and IL-1 lethality.

Defective Tolerance to the Toxic and Metabolic Effects of Interleukin 1

Endocrinology, Mar 1, 1991

Abstract The effect on food intake, body weight, and survival of mice given recombinant lipopolys... more Abstract The effect on food intake, body weight, and survival of mice given recombinant lipopolysaccharide (LPS), tumor necrosis factor/cachectin (TNF), or interleukin 1 (IL-1)(5 μg/mouse, ip, twice daily) was studied. All agents induced a rapid reduction of food intake ...

Cytokine down-regulation in endotoxin tolerance

PubMed, Mar 1, 1993

Cytokine production is down-regulated in LPS tolerance. 1) This down-regulation has been reported... more Cytokine production is down-regulated in LPS tolerance. 1) This down-regulation has been reported in various animal species and cell types, and can be induced both in vivo and in vitro (indicating a desensitization of the cytokine-producing cells). 2) It can also be induced in humans in vivo and in vitro. 3) It is reversible, since the refractory state can be bypassed by administering LPS along with IFN-gamma or PMA. 4) Under certain conditions, it is specific since cytokines will still be induced in response to non-LPS stimuli (Staphylococcus, zymosan, MDP), meaning a real LPS-desensitization is involved rather than an aspecific blockade of cytokine synthesis. 5) in vivo, due to the complexity of the system, other factors than a simple desensitization of cytokine-producing cells contribute to LPS tolerance (aspecific blockade of cytokine synthesis, corticosteroid-dependent feedback, increased clearance by RES and changes in macrophage populations, inhibitory cytokines.

Molecular Medicine, Jun 25, 2020

Proteins released in glutathionylated form

PLOS ONE, May 18, 2015

<p>Proteins in the NEM-blocked supernatants from BioGEE-pretreated, LPS-stimulated cells we... more <p>Proteins in the NEM-blocked supernatants from BioGEE-pretreated, LPS-stimulated cells were immunoprecipitated with anti-PRDX1 (A) or anti-TXN1 (B). Immunoprecipitated proteins were run under non-reducing (two lanes on the left) or reducing conditions (the two lanes with DTT, on the right). Proteins were then visualized by Western blot with streptavidin peroxidase. The same blot was stripped and reprobed with anti-PRDX1 or anti-TXN1 antibody to locate the proteins (left, in both A and B). m, monomer; d, dimer.</p

Inhibition by interleukin 1 receptor antagonist of in vivo activities of interleukin 1 in mice

PubMed, Oct 1, 1991

A polypeptide homologous to IL-1, with antagonistic activity (IL-1ra), has recently been describe... more A polypeptide homologous to IL-1, with antagonistic activity (IL-1ra), has recently been described. Given the pleiotropic activity of interleukin (IL-1) it is important to establish the spectrum of inhibitory activity of IL-1ra on in vivo action of IL-1. We tested the effect of IL-1ra on IL-1 induced lethality in adrenalectomized mice, hypoglycemia, and induction of serum corticosterone and interleukin 6. Administration of IL-1ra (200 micrograms/mouse) protected adrenalectomized mice against the lethal effect of 1 microgram of IL-1. IL-1ra at 20 micrograms/mouse completely blocked induction of IL-6 and markedly inhibited hypoglycemia and increase in serum corticosterone induced by 0.1 micrograms of IL-1. These data indicate that IL-1ra inhibits the action of IL-1 on different target tissues involved in the various actions of IL-1 in vivo.

Journal of NeuroVirology, 2000

Human immunode®ciency virus (HIV) infection of the central nervous system (CNS) affects primarily... more Human immunode®ciency virus (HIV) infection of the central nervous system (CNS) affects primarily microglial cells and astrocytes. Infection of these latter cells occurs independently of CD4 and is characterised by preferential accumulation of 2 Kb mRNA, encoding mostly Nef, and by low levels of 4.5 and 9 Kb RNAs. We have investigated the potential role of chronic HIV infection of human astrocytic cells on the expression of pro-in¯ammatory cytokines, chemokines and their receptors by comparing the infected TH4-7-5 with its parental uninfected 85HG66 cell lines. Upregulated levels of tumour necrosis factor-a (TNF-a) and of certain chemokines, namely interleukin-8 (IL-8) and regulated upon activation normal T cell expressed and secreted (RANTES), were observed in the infected versus uninfected cells, whereas monocyte chemotactic protein-1 (MCP-1) was comparably expressed in both cell lines. This pattern of expression was con®rmed in primary foetal astrocytes transiently transfected with HIV. In addition, CXCR1, CXCR2 and CCR2b, receptors for IL-8 and MCP-1, respectively, were also found to be upregulated in TH4-7-5 versus 85HG66. CXCR4, the receptor of stromal cell derived factor-1 (SDF-1) and co-receptor for syncytium inducing HIVs, was comparably expressed in infected and uninfected astrocytic cells, whereas CCR5 was not detected in either cell line. Furthermore, treatment of TH4-7-5 cells with TNF-a or IL-1b stimulated RNA and protein secretion of IL-8, MCP-1, and RANTES as well as HIV expression. Thus, our ®ndings suggest that HIV infection of astrocytic cells can contribute to the establishment of a chronic in¯ammatory state in the CNS, eventually resulting in HIV encephalitis, by increasing the secretion of pro-in¯ammatory cytokines, such as TNF-a and several chemokines. Overexpression of chemokine receptors including CCR2b, CXCR1 and CXCR2 in infected astrocytic cells may contribute to HIV-induced damage of the CNS via autocrine/paracrine activation of astrocytes.

Molecular Medicine, Apr 9, 2020

Background: Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it ... more Background: Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation. Methods: Gene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction to p-values, and significant genes were grouped into coexpression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package. Results: Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. Conclusions: This study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.

bioRxiv (Cold Spring Harbor Laboratory), Aug 9, 2019

Tumor Necrosis Factor-Α Drives HIV-1 Replication in U937 Cell Clones and Upregulates CXCR4

Cytokine, 2001

Blood, Mar 15, 1999

グルタチオンはその抗酸化特性と独立してマクロファージ細胞株における抗ウイルス経路に対する自然免疫応答を調整する【JST・京大機械翻訳】

Frontiers in Immunology (Web), 2017

Proceedings of the National Academy of Sciences of the United States of America, Jul 25, 2000

Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells

European Journal of Immunology, Feb 1, 1993

Journal of Virology, Nov 1, 2002

CHEMOKINES Human Immunodeficiency Virus Replication Induces Monocyte Chemotactic

Serum Amyloid a Induction in Tumor-Bearing Mice-Evidence for a Tumor-Derived Mediator

Proceedings of the National Academy of Sciences of the United States of America, Sep 18, 2001

Reversal of defective IL-6 production in lipopolysaccharide-tolerant mice by phorbol myristate acetate

Journal of Immunology, Aug 1, 1991

Proteins identified from BioGEE-treated samples

PLOS ONE, May 18, 2015

<p>Proteins identified from BioGEE-treated samples.</p

International Journal of Immunopharmacology, 1991

Defective Tolerance to the Toxic and Metabolic Effects of Interleukin 1

Endocrinology, Mar 1, 1991

Cytokine down-regulation in endotoxin tolerance

PubMed, Mar 1, 1993

Molecular Medicine, Jun 25, 2020

Proteins released in glutathionylated form

PLOS ONE, May 18, 2015

Inhibition by interleukin 1 receptor antagonist of in vivo activities of interleukin 1 in mice

PubMed, Oct 1, 1991

Journal of NeuroVirology, 2000

Molecular Medicine, Apr 9, 2020