Am. J. Respir. Cell Mol. Biol., Volume 24, Number 1, January, 2001 74-82

Reduced Interferon- Secretion by Natural Killer Cells from Rats Susceptible to Postviral Chronic Airway Dysfunction

Lance D. Mikus, Louis A. Rosenthal, Ronald L. Sorkness, and Robert F. Lemanske Jr.

Division of Allergy, Departments of Medicine and Pediatrics, and School of Pharmacy, University of Wisconsin, Madison, Wisconsin

After parainfluenza type 1 (Sendai) virus infection as weanlings, Brown Norway (BN), unlike Fischer 344 (F344), rats develop an asthma-like phenotype. Reduced postinfection interferon (IFN)- levels in bronchoalveolar lavage fluid from BN weanlings and the prevention of chronic airway sequelae in BN rats by IFN- treatment led to the hypothesis that cells from BN weanlings have a reduced ability to secrete IFN-. After stimulation with Sendai virus or interleukin (IL)-12, splenocytes from uninfected BN weanlings secreted significantly less IFN- than did splenocytes from F344 weanlings (P < 0.005), as determined by enzyme-linked immunosorbent assay. Because levels of potential IFN--secreting cells in the spleen differed between the strains, natural killer (NK) cells, an important IFN- source during early antiviral responses, were purified from spleens of uninfected weanlings. When stimulated with IL-12, BN NK cells secreted significantly less IFN- than did F344 NK cells (P < 0.001). Incubation of NK cells from either strain with IL-12 and IL-18 resulted in synergistic increases in IFN- production, but BN cells still secreted significantly less IFN- than did F344 cells (P < 0.05). Similarly, after incubation with either IFN- or IFN- plus IL-18, BN NK cells secreted significantly less IFN- than did F344 NK cells (P < 0.05). Therefore, reduced IFN- secretion by NK cells in BN weanlings may play a role in the development of postviral chronic airway dysfunction.

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