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      Inflammatory cytokines and inhibitors in HIV infection: correlation between interleukin-1 receptor antagonist and weight loss.

      AIDS (London, England)

      Weight Loss, Acquired Immunodeficiency Syndrome, complications, immunology, Adult, CD4 Lymphocyte Count, Cachexia, etiology, Cytokines, blood, Female, HIV Core Protein p24, analysis, HIV Seropositivity, Humans, Interleukin 1 Receptor Antagonist Protein, Interleukin-1, Male, Prospective Studies, Receptors, Interleukin-1, antagonists & inhibitors, Recombinant Proteins, Sialoglycoproteins

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          To determine serum levels of the interleukin-1 receptor antagonist (IL-1Ra), together with cytokines, other cytokine inhibitors and markers of immune activation in HIV-infected patients. Sixty-one HIV-patients were classified into Center for Disease Control and Prevention (CDC) groups A (n = 14), B (n = 14) and C (n = 33). Serum levels of IL-1Ra, IL-1 beta, IL-6, tumour necrosis factor (TNF-alpha, TNF soluble receptors (TNF-sR) and IL-2sR were measured by enzyme-linked immunosorbent assay. CD4+ cell counts, p24 antigen, immunoglobulin (Ig) A, beta 2-microglobulin, triglycerides and neopterin were measured according to standard procedures. Weight variation was measured as the percentage of baseline weight lost or gained during the 3 months before sampling. Serum levels of IL-1Ra were significantly elevated in HIV-infected patients, compared with control subjects (S47 +/- 104 and 133 +/- 7 pg/ml), but did not vary significantly with the HIV disease stage, CD4+ cell count or p24 antigenaemia. IL-1Ra levels correlated with IL-1 beta (P < 0.005), IL-6 (P < 0.0001) and TNF-sR55 (P < 0.0001) levels, but not with those of TNF-alpha, TNF-sR75, IL-2sR, neopterin or IgA. IL-1 Ra and IL-1 Ra/IL-1 beta ratio were the only parameters significantly elevated (R = -0.67, P < 0.0001) in the HIV-infected patients with marked weight loss (n = 12; mean of weight variation, -13.9 +/- 2.1% relative to the other patients, regardless of HIV disease stage and opportunistic infections. IL-1Ra levels are significantly elevated in HIV infected patients, independently of immune deficiency. We propose that IL-1Ra accumulates in intense systemic inflammation, a state which does not seem to be reflected by the elevation of a single cytokine or the activation at a single cell system and which is correlated with marked weight loss.

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