IL-10 neutralization augments mouse resistance to systemic Mycobacterium avium infections

In this contribution, we examined the involvement of the cytokine IL-10 in the progression of experimental murine Mycobacterium avium infections in susceptible BALB/c mice. Addition of anti-IL-10 antibodies in the supernatants of peritoneal macrophages infected with virulent M. avium resulted in a significantly enhanced mycobacteriostatic activity of macrophages. In BALB/c mice infected with the B101 or B102 virulent M. avium strains, examination of the cytokine release profile in splenocytes from infected mice showed that infection was associated with an initial copious release of both IFN-gamma and IL-10. IL-10 production increased as the infection progressed, whereas IFN-gamma levels diminished. Infected mice were given repeated infusions of a rat mAb against mouse IL-10 or rat IgM. Examination of IgM serum levels in anti-IL-10-treated mice (infected or not) showed that depletion of endogenous IL-10 resulted in much decreased IgM levels. Results showed that infusions of large dosages of the monoclonal anti-IL-10 resulted in a very significantly diminished bacterial growth in the spleens. These findings indicate that IL-10 may have a negative impact on resistance to M. avium infections, due, at least in part, to decreased macrophage activity.