M. Petrofsky et Le. Bermudez, Neutrophils from Mycobacterium avium-infected mice produce TNF-alpha, IL-12, and IL-1 beta and have a putative role in early host response, CLIN IMMUNO, 91(3), 1999, pp. 354-358
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.