Generation of Cytokines in Human Visceral Leishmaniasis: Dissociation of Endogenous TNF-α and IL-1β Production

Abstract

The role of TNF-α in visceral leishmaniasis is ambivalent, the eventual outcome of this infection, cure or generalization, being determined by the relative amounts of cytokines produced in vivo. Since release, by monocytes/macrophages, of TNF-α and interleukins 1β (IL-1β) and IL-6 is important in both the induction and effector phases of the immune responses, these mediators were determined in sera and cell culture supernatants of seventeen L. donovani infected patients in Brazil. The results are compared to those of a local control group. Circulating immunoreactive TNF-α in patients (median, 140 pg ml -1) was increased ten-fold over controls (median 16 pg m1 -1, p≤0.0001). In contrast, serum IL-1β was <20 pg ml -1 in all patients, although detectable in sera of 3/16 Brazilian controls (chi 2=3.5, p<0.1). Mitogen induced in vitro release of IL-1β and IL-6 by patients' circulating mononuclear cells was significantly reduced, and the capacity of patients' peripheral monocytes for H 2O 2 generation in response to opsonized zymosan was significantly diminished. In the patients, serum TNF-α levels were inversely related to IL-1β release in vitro (rho=-0.57, p≤0.01).