Cytokine patterns in adults with AIDS

Background: It has been reported that in HIV infected patients enhanced production of IL-4 and IL-10 in response to stimulation of peripheral blood lymphocytes with phytohemagglutinin is associated with disease progression. Some have proposed that a switch from a cytokine profile associated with CD4+ Th1 predominance (IL-2, IFN-G, TNF-B) to Th2 preddominance (IL-4, IL-5) plays a major role in the progression of HIV infection. Others find no clear evidence for the dichotomy of Th1 and Th2 predominance in HIV infected patients Discrepant results have been reported in, studied populations in which only a few cytokines have been examined. Methods: Thirty-one adult patients with AIDS but without other active infections provided serum and peripheral blood lymphocytes for determination of cytokine levels. Their responses were compared to those of five normal healthy volunteers without active infection. ELISA techniques were employed to quantitate cytokine levels. Both circulating lymphocyte and enriched lymphocyte populations were studied with and without stimulation employing phytohemagglutinin and/or rhIL-2. Results: Patterns of cytokine expression were analyzed in 31 adult patients with AIDS but without other active infections. All had CD4+ cell counts below 50 and large viral loads (Roche PCR). The unstimulated cytokine profile in these patients generally showed marked elevations in IL-1, IL-3, IL-4, IFN-G, TNF-A, TNF-B, OSM and TGF-B. Minimal elevations compared to normal healthy volunteers were noted for IL-2, IL-6, IL-8, IL-12, IFN-A and IL-6SR. The levels of RANTES were lower than in normal healthy volunteers. Responses of peripheral blood lymphocytes to stimulation with phytohemagglutinin showed enhancement of all cytokines in all subjects studied though the response was much less marked in AIDS patients than in normal volunteers with the exception of IL-3, IL-4, IL-8, TNF-B, and TGF-B which are increased. Little difference in IL-2 and IL-12 expression was noted between stimulated peripheral blood lymphocytes of AIDS patients and normal healthy volunteers. No relation was noted with patient age or with any use of antiretroviral agents. Recombinant human IL-2 was a less potent stimulant than was phytohemagglutinin. Conclusion: The character of cytokine response in AIDS patients may be directly related to the stimulus employed in test systems. There is no evidence for Th1/Th2 dysregulation. Cytokine elevations in AIDS patients generally are reflective of chronic infection (the virus). Lymphocytes from AIDS patients do not respond as well to stimulation as do those from normal healthy volunteers. The stimulated lymphocyte response in AIDS patients suggests there is underlying low-grade host versus virus reaction in these patients (exaggerated responses of IL-3, IL-4, IL-8, TGF-B).