PENTOXIFYLLINE IMPAIRS MACROPHAGE DEFENSE AGAINST MYCOBACTERIUM-AVIUMCOMPLEX

Pentoxifylline, a tumor necrosis factor-alpha (TNF) inhibitor, is bein g tested as a treatment adjunct in human immunodeficiency virus (HIV)- infected patients. However, TNF is important in cellular defense. The effect of pentoxifylline on Mycobacterium avium complex (MAC) growth i n exogenously infected macrophages was compared with the effect of dex amethasone. Pentoxifylline, in a concentration that decreased MAC-indu ced TNF by 48.1%, enhanced MAC growth by 1.9- to 19.6-fold and 1.82- t o 4.46-fold in macrophages from normal and HIV-infected patients, resp ectively, It also induced interleukin-6 (IL-6) in infected macrophages , IL-6 induction correlated with the increase in MAC growth (y = 0.89 + 0.266x, P = .025), Dexamethasone in an equivalent TNF-suppressing co ncentration also increased MAC growth but was less effective, Unlike p entoxifylline, dexamethasone suppressed IL-6 and the suppression corre lated inversely with MAC growth (y = 0.248 + 9.942x, P = .003). Thus, TNF and IL-6 are important in macrophage defense against MAC. Pentoxif ylline and dexamethasone should be used with caution in AIDS patients.