Neutrophils from Mycobacterium avium-infected mice produce TNF-alpha, IL-12, and IL-1 beta and have a putative role in early host response

Recent evidence supports a role for neutrophils in the host defense against Mycobacterium avium. To determine whether the depletion of neutrophils has an effect on the outcome of infection in mice as determined by the number of bacteria in liver and spleen, we administered RB6-8C5 anti-neutrophil an tibody intraperitoneally both early and late in the infection. Mice were th en observed for 14 days and harvested. The number of viable bacteria in liv er and spleen was determined. While administration of RB6-8C5 antibody earl y in infection resulted in a significant increase in the number of bacteria in organs when compared with mice receiving immunoglobulin control, admini stration of RB6-8C5 antibody late in infection (week 3) did not have an imp act on the bacterial load in tissue. Infection of CD18 knockout mice (with impaired neutrophil function), however, did not show a significant enhancem ent of M. avium growth when compared with that of wild-type control mice. N eutrophils were found to produce increased amounts of TNF-alpha and IL-12 a nd IL-1 than control uninfected mice during the initial phase of infection, but not after 2 weeks following infection (although IL-1 beta levels conti nue elevated). The results suggest that neutrophils may have a role in the early (innate) immune response against M. avium but it is only evident afte r acute depletion of neutrophils and not in mice with chronic neutrophil im pairment. (C) 1999 Academic Press.