CYTOKINE PATTERNS IN ADULTS WITH AIDS

Background: It has been reported that in HIV infected patients enhance d production of IL-4 and IL-10 in response to stimulation of periphera l 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 pre ddominance (IL-4, IL-5) plays a major role in the progression of HIV i nfection. Others find no clear evidence for the dichotomy of Th1 and T h2 predominance in HIV infected patients Discrepant results have been reported in, studied populations in which only a few cytokines have be en examined. Methods: Thirty-one adult patients with AIDS but without other active infections provided serum and peripheral blood lymphocyte s for determination of cytokine levels. Their responses were compared to those of five normal healthy volunteers without active infection. E LISA techniques were employed to quantitate cytokine levels. Both circ ulating lymphocyte and enriched lymphocyte populations were studied wi th and without stimulation employing phytohemagglutinin and/or rhIL-2. Results: Patterns of cytokine expression were analyzed in 31 adult pa tients with AIDS but without other active infections. All had CD4+ cel l 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 eleva tions 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 i n normal healthy volunteers. Responses of peripheral blood lymphocytes to stimulation with phytohemagglutinin showed enhancement of all cyto kines 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 b lood lymphocytes of AIDS patients and normal healthy volunteers. No re lation was noted with patient age or with any use of antiretroviral ag ents. Recombinant human IL-2 was a less potent stimulant than was phyt ohemagglutinin. Conclusion: The character of cytokine response in AIDS patients may be directly related to the stimulus employed in test sys tems. There is no evidence for Th1/Th2 dysregulation. Cytokine elevati ons in AIDS patients generally are reflective of chronic infection (th e virus). Lymphocytes from AIDS patients do not respond as well to sti mulation as do those from normal healthy volunteers. The stimulated ly mphocyte response in AIDS patients suggests there is underlying low-gr ade host versus virus reaction in these patients (exaggerated response s of IL-3, IL-4, IL-8, TGF-B).