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

Abstract

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.