Modulation of immune responses in mice by oral administration of niflumic acid

The in vivo effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the host immune system are still poorly understood. However, through inhibition of prostaglandin synthesis, NSAIDs may exhibit immunomodulating properties. The present work was aimed at evaluating the influence of niflumic acid on immune responses when administered orally for 7 consecutive days to 8-week-old inbred mice. Immunological tests were performed 24 h after the arrest of the treatment. At a dosage of 50 mg/kg/day, niflumic acid exerted noticeable immunostimulating effects, as shown by an increase in plaque-forming cell numbers after in vivo immunization with sheep red blood cells, an augmentation of spleen cell proliferation responses to stimulation with T- or B-cell mitogens and of T-cell cytotoxic response to allogenic cells. Phagocytosis-induced chemiluminescence of peritoneal macrophages was also enhanced whereas interleukin-1 production by these cells was depressed, but without concomitant modification in interleukin-2 production by T-cells. Increasing the niflumic acid dosage to 75 mg/kg resulted in the disappearance of the immunostimulatory effects on lymphocytes responses. Macrophage activities were affected similarly in mice receiving 50 mg/kg. These results demonstrate that niflumic acid is able to stimulate in vivo several immunological functions and, consequently, to maintain host immune defenses. Interestingly, it depressed interleukin-1 production, known to play a major role in the inflammatory process.