Pentoxifylline impairs macrophage defense against Mycobacterium avium complex

Pentoxifylline, a tumor necrosis factor-alpha (TNF) inhibitor, is being 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 in exogenously infected macrophages was compared with the effect of dexamethasone. Pentoxifylline, in a concentration that decreased MAC-induced TNF by 48.1%, enhanced MAC growth by 1.9- to 19.6-fold and 1.82- to 4.46-fold in macrophages from normal and HIV-infected patients, respectively. 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 concentration also increased MAC growth but was less effective. Unlike pentoxifylline, dexamethasone suppressed IL-6 and the suppression correlated inversely with MAC growth (y = 0.248 + 9.942x, P = .003). Thus, TNF and IL-6 are important in macrophage defense against MAC. Pentoxifylline and dexamethasone should be used with caution in AIDS patients.