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Ralph H. Johnson Veterans Affairs Medical Center and the Medical University of South Carolina, Charleston, SC 29425;
Durham Veterans Affairs Medical Center and Duke University Medical Center, Durham, NC 27705; and
Section of Retroviral Research, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Microbial DNA has multiple immune effects including the capacity to
induce polyclonal B cell activation and cytokine production in normal
mice. We recently described the accelerated induction of anti-DNA
Abs in NZB/NZW mice immunized with Escherichia coli (EC)
dsDNA; paradoxically these mice developed less renal disease than
unimmunized mice or mice immunized with calf thymus DNA. We postulated
that alterations in cytokine production induced by bacterial DNA may
play a key role in renal protection. To determine the effect of
bacterial DNA on cytokine production in NZB/NZW mice, we measured the
serum cytokine levels, cell culture supernatant cytokine levels, and
number of cytokine-producing splenocytes in NZB/NZW mice injected with
EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was
a 10- to 25-fold increase in the number of cells secreting IFN-
compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells
were also increased by bacterial DNA immunization. In parallel with the
increase in IFN- secreting cells, there was a significant rise in
serum IFN- levels in mice receiving EC DNA. These results indicate
that EC DNA modulates systemic cytokine levels in NZB/NZW mice,
selectively increasing IL-12 and IFN- while decreasing IL-4
production. The cytokine response of NZB/NZW mice to bacterial DNA may
be of significance in disease pathogenesis and relevant to the
treatment of lupus-like disease.
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