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Effect of cyclosporin A on murine experimental salmonellosis
S Muthukkumar1, V Muthukkaruppan
1Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, India.
Abstract:
Investigations were undertaken to evaluate the effect of cyclosporin A (CyA) on primary infection of mice with Salmonella typhimurium. Further, its effect on delayed-type hypersensitivity (DTH) and antibody response to porin, an outer membrane protein of S. typhimurium, has been characterized under different CyA regimen. When mice were infected i.p. with 5 x 10(4) live medium virulent organisms, the bacterial growth increased by about 2 log10 in CyA treated mice. CyA administered daily for 2 weeks following immunization with porin caused profound suppression of DTH and both IgM and IgG antibody responses. Given a single dose of CyA 24 h before DTH elicitation, the drug had a marked suppressive effect on DTH, but not on the antibody response to porin. Treatment on days 0-5 following immunization had no effect on the manifestation of the DTH response nor on the anti-porin IgM response whereas an enhanced level of IgG was observed in this group.
Insights
Cyclosporin A (CyA) treatment increased Salmonella typhimurium bacterial growth in mice. CyA also suppressed delayed-type hypersensitivity (DTH) and antibody responses to porin, with varied effects based on drug regimen.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Salmonella typhimurium is a significant bacterial pathogen.
- Cyclosporin A (CyA) is an immunosuppressive drug with potential impacts on infection and immunity.
- Porin is a key outer membrane protein of S. typhimurium involved in immune responses.
Purpose of the Study:
- To investigate the effect of Cyclosporin A (CyA) on primary Salmonella typhimurium infection in mice.
- To characterize the impact of different CyA treatment regimens on delayed-type hypersensitivity (DTH) and antibody responses to S. typhimurium porin.
Main Methods:
- Mice were infected intraperitoneally with live S. typhimurium.
- CyA was administered at various time points relative to immunization and infection.
- Bacterial growth, DTH responses, and specific IgM and IgG antibody titers to porin were measured.
Main Results:
- CyA treatment led to a significant increase (approximately 2 log10) in bacterial growth following S. typhimurium infection.
- Daily CyA administration for two weeks post-porin immunization profoundly suppressed DTH, IgM, and IgG antibody responses.
- A single CyA dose before DTH elicitation suppressed DTH but not antibody response; treatment during early immunization days (0-5) suppressed DTH and IgM but enhanced IgG response.
Conclusions:
- Cyclosporin A exacerbates S. typhimurium infection in mice.
- The timing and duration of CyA administration significantly influence its immunosuppressive effects on DTH and antibody production against S. typhimurium porin.
- CyA's differential impact on IgM and IgG responses suggests complex modulation of B cell immunity.