Cytomegalovirus (CMV) is a major cause of morbidity and mortality among immunocompromised patients and improved therapies are urgently needed. Manipulation of cytokines represents a potential immunomodulatory approach to treatment of CMV infection. To define cytokine responses during CMV infection, we studied serum cytokine concentrations in succeptible Balb/c mice and relatively resistant C57BL/6 mice after injection with murine CMV (MCMV). Serum interferon-γ (IFN-γ) levels peak at Day 2 in resistant C57BL/6 mice, but IFN-γ responses are delayed in susceptible Balb/c mice with peaks occuring at Day 6-7. IL-12 is detected in the serum of both Balb/c and C57BL/6 mice by Day 2, suggesting that the delay in IFN-γ production in Balb/c mice is not due to delayed or defective IL-12 signaling. Pro-inflammatory cytokines including TNF-α, IL-1, and IL-6 are produced early after MCMV infection with peak serum levels appearing by Day 2 in both groups of mice. IL-10 levels peak later in the course of MCMV infection, after serum concentrations of the proinflammatory cytokines begin to decrease. IL-2 (reflecting Th-1) and IL-4 (reflecting Th-2) type cytokines are not detected. Serum TGF-β levels decrease from baseline levels in both Balb/c and C57BL/6 mice, with nadir levels observed on Day 3-4, corresponding to peaks of the proinflammatory cytokines. In summary, macrophage derived cytokines, including IL-12, are produced early in MCMV infection in both Balb/c and C57BL/6 mice. Strain differences in susceptibility to MCMV may be attributable to differential IFN-γ production. Th-1 and Th-2 type cytokines do not appear to play a major role in the response to MCMV. We conclude that MCMV infection is accompanied by a characteristic pattern of cytokine responses. These observations provide a basis for the development of potential immunomodulatory therapies which may eventually prove useful for treatment of human CMV disease.
|Original language||English (US)|
|Number of pages||1|
|Journal||Clinical Infectious Diseases|
|State||Published - 1997|
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