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The effect of nisin on the immune response of mice was studied. Nisin (in the form of the commercial preparation Nisaplin) was incorporated in the diet of experimental mice which were fed for 30, 75 or 100 days. Short-term administration of diets containing Nisaplin induced an increase of both CD4 and CD8 T-lymphocyte cell counts and also a decrease of B-lymphocyte counts. After prolonged diet administration, T-cell counts returned to control levels. Normal levels of B-lymphocytes were also reached after prolonged administration of the lower (but not the higher) Nisaplin concentration. The macrophage/monocyte fraction isolated from peripheral blood became significantly increased after long-term administration (100 days) of Nisaplin-containing diets in a concentration-dependent way. Although the number of peritoneal cells was not affected by the diets, the phagocytic activity of peritoneal cells decreased after prolonged administration of low (but not high) Nisaplin doses.

The effect of several Campylobacter jejuni strains on the immune response was analyzed in mice after intraperitoneal inoculation with 10(10) colony forming units (CFU). Three C. jejuni strains were assayed: CCUG 6968 (enterotoxigenic), CCUG 7580 (enterotoxigenic), and CCUG 7440 (non-enterotoxigenic). These C. jejuni strains induced a peritoneal inflammatory response and an important increase in the peritoneal phagocyte oxidative activity measured by chemiluminescence assay, as well as an increase in the number of peritoneal cells. Both interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) production by peritoneal cells were not modified. However, C. jejuni 7440 caused a statistically significant increase in TNFalpha production. These results have demonstrated that different strains of C. jejuni induce an increase of the inflammatory response without a significant cytokine release. However, these infectious microorganisms may be eliminated efficiently by murine macrophages after phagocytosis.

Campylobacter jejuni has been reported to produce different toxins that may modulate the immune response in both animals and humans. The effect of C. jejuni enterotoxin on the immune response was investigated in two groups of Balb/c mice. One of them was inoculated intraperitoneally with 1010 colony forming units (CFU) of an enterotoxigenic strain (CCUG 7580), and the second one with a non-enterotoxigenic strain (CCUG 7440). The number of polymorphonuclear (PMN) cells from spleen increased in both enterotoxigenic and non-enterotoxigenic strains as a consequence of C. jejuni infection. Notwithstanding, lymphocyte proliferation stimulated by lipopolysaccharide (LPS) was increased by both enterotoxigenic and non-enterotoxigenic strains. Interleukin-2 (IL-2) production from splenic cells was increased significantly by infection with the enterotoxigenic strain. Both enterotoxigenic and non-enterotoxigenic strains reduced the splenic response to sheep erythrocytes; the response was significantly suppressed for immunoglobulin M (Ig M) and for immunoglobulin G (Ig G) synthesis. These results suggest that C. jejuni is able to modify some components of the immune response in mice, and also that the enterotoxigenic strain has more immunomodulating activity than the non-enterotoxigenic strain.

After intraperitoneal inoculation with Campylobacter jejuni BALB/c, Swiss and DBA mice show a peritoneal inflammatory response of different intensity. Only BALB/c mice have a strong peritoneal response. Simultaneous intraperitoneal inoculation of C. jejuni plus FeCl3 increase both inflammatory response and phagocytic activity in Swiss mice, without production of diarrhea. Some thermostable compounds of C. jejuni have a very strong chemotactic activity against peritoneal cells of mice, whereas a diffusible, thermolabile and glutaraldehyde-resistant factor has an inhibitory effect over murine peritoneal cell phagocytosis. Bactericidal activity of peritoneal cells increased after in vitro re-challenge with C. jejuni. Bacteremia is present in all the mice strains tested, but the clearance is quick in DBA and slow in BALB/c and Swiss mice. These experiments confirm that in mice, peritoneal non-specific mechanisms of defense, such as macrophages, play an important role in order to control C. jejuni infection.

The immunomodulating properties of antimicrobial drugs may have important implications for clinical practice, particularly for those patients whose immune system has been compromised. In this study, we assessed the influence of different treatments with a beta-lactam antibiotic (imipenem/cilastatin) on several acquired immune responses of BALB/c mice; splenocyte responses to specific mitogens and to sheep red blood cells, IL-2 production and proportions of the different lympho-monocytic populations. Impenem/cilastatin was shown to modify some lymphocyte-associated immune functions and it would be useful to investigate whether immunomodulatory effects also occur in humans.

The imipenem/cilastatin constitutes a broad spectrum /Mactam antibiotic formulation, especially used in pre and post-operatory treatments for transplanted or drug-immunosuppresedpatients. The effect of the dose and the duration of the treatment with imipenem/cilastatin on someparameters of natural immunity in BALB/cmice were examined. The treatment by intraperitoneal route with i or 2 g/70 kg/day during 7 days did not alter significantly the parameters tested, whereas the greater dose used (4 g/70 kg/day) had an inhibitory effect on peritoneal cell counts and phagocytic activity, as well as it caused an increase on IL-1 production and natural killer activity. The greater stimulating effect of innate immunity was obtained with the lowest imipenem/cilastatin dose used (0.5 g/70 kg/day). Since this antibiotic apparently does not impair the studied innate immune responses at 1 or 2 g/70kg/day, it seems to be especially suited for the therapy of systemic bacterial infections in immunocompromisedpatients.