POSSIBLE PARTICIPATION OF POLYMORPHONUCLEAR CELLS STIMULATED BY MICROBIAL IMMUNOMODULATORS IN THE DYSREGULATED CYTOKINE PATTERNS OF AIDS PATIENTS

Macrophages and polymorphonuclear cells (PMN) play a major role as cel ls primarily responsive to microbial biological response modifiers (BR M), Although much attention has been given to macrophages, PMN have be en relatively underinvestigated. We have recently studied the response s of PMN from HIV- and HIV+ subjects after stimulation with a powerful immunomodulatory fraction from the cell wall of Candida albicans (MP- FB) and compared this to bacterial lipopolysaccharide (LPS), Both cyto kine patterns and PMN anticandidal activity were investigated, MP-F2, like LPS, was an active inducer of interleukin-8 (IL-8), tumor necrosi s factor alpha (TNF-alpha), IL-6, and IL-1 beta production by PMN and monocytes from all subjects, IL-12 was also produced by MP-F2-stimulat ed PMN in the presence of interferon-gamma (IFN-gamma), PMN from HIVsubjects showed increased in vitro expression of TNF-alpha and IL-6 ge nes as determined by semiquantitative reverse transcriptase-polymerase chain reaction, In all subjects, cytokine gem expression was strongly stimulated by MP-FP or LPS and inhibited by IL-10, Production of IL-6 and TNF-alpha protein (measured by ELISA) was higher in PMN from HIV subjects in at least one of the conditions tested (unstimulated or st imulated by LPS or MP-F2), However, the amount of the C-X-C chemokine IL-8 was equal in PMN from HIV- and HIV+ subjects, PMN from HIV+ subje cts were at least as active in inhibiting candide growth as PMN from H IV- controls, In both groups PMN were equally stimulated by MP-FB and LPS, Only in severely neutropenic subjects was there some reduction in the anticandidal activity but not in cytokine responses, When appropr iately stimulated by microbial BRM, PMN are active producers of pro-in flammatory and immunomodulatory cytokines, This production is not only totally preserved in HIV+ subjects but may be higher than in PMN from HIV- subjects and may be coupled with an efficient anticandida activi ty, We suggest that during common bacterial or fungal infections PMN m ay contribute to the dysregulated production of inflammatory cytokines in AIDS patients.