The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity.

The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated. Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation. Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines. It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity. The present study confirms these observations. A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction. Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine.

The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants.

The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell ELISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25-kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon-gamma (IFN-gamma) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25-kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25-kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function.