Immunomodulatory activities of gemifloxacin in mice

Document Type: Original Article

Authors

1 Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan

2 University Diagnostics Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan

Abstract

Objective(s):Gemifloxacin is a broad spectrum antibiotic and has shown excellent coverage against a wide variety of microorganisms. In this study, an attempt was made to evaluate the immunomodulatory potential of gemifloxacin in male swiss albino mice in vivo.
Materials and Methods: Three doses of gemifloxacin 25 mg/kg, 50 mg/kg and 75 mg/kg were used intraperitoneally (IP) for the evaluation of immune responses in mice. Delayed type hypersensitivity (DTH), heamagglutination assay, jerne hemolytic plaque formation assay and cyclophosphamide induced neutropenia assay were performed to evaluate the effect of gemifloxacin on immune responses.
Results: DTH assay has shown the significant immune suppressant potential of gemifloxacin at 25 mg/kg dose and 75mg/kg dose. Total leukocyte count (TLC) has shown decrease in leukocyte count (P<0.05) in drug treatment groups before cyclophosphamide administration and significant decrease (P<0.001) in leukocyte count after cyclophosphamide administration as compared to negative control group. Differential leukocyte count (DLC) has shown significant decrease (P<0.001) in percentage count of lymphocytes in 75 mg/kg treatment group in leukopenic mice while increase (P<0.01) in monocytes percentage in 50 mg/kg treatment group in leukopenic mice and increase in neutrophil percentage count (P<0.05) in all treatment groups was observed after cyclophosphamide administration. Humoral immune response is shown to be suppressed in dose dependent manner by both heamagglutination titre values (P<0.001) and jerne hemolytic plaque formation assay (P<0.001).
Conclusion: The results of this work clearly demonstrate that gemifloxacin has significant immunomodulatory potential.

Keywords


1. Wispelwey B, Schafer KR. Fluoroquinolones in the management of community-acquired pneumonia in primary care. Expert Rev Anti Infect Ther 2010; 8:1259-1271.

2. Albertson TE, Dean NS, El Solh AA, Gotfried MH, Kaplan C, Niederman MS. Fluoroquinolones in the management of community‐acquired pneumonia. Int J Clin Pract 2010; 64:378-388.

3. Bearden DT, Danziger LH. Mechanism of action of and resistance to quinolones. Pharmacotherapy 2001; 21:224S-232S.

4. Heaton VJ, Ambler JE, Fisher LM. Potent antipneumococcal activity of gemifloxacin is associated with dual targeting of gyrase and topoisomerase IV, an in vivo target preference for gyrase, and enhanced stabilization of cleavable complexes in vitro. Antimicrob Agents Chemother 2000; 44:3112-3117.

5. Yague G, Morris JE, Pan XS, Gould KA, Fisher LM. Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob Agents Chemother 2002; 46:413-419.

6. Saravolatz LD, Leggett J. Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquino-lones. Clin Infect Dis 2003; 37:1210-1215.

7. Dalhoff A, Shalit I. Immunomodulatory effects of quinolones. Lancet Infect Dis 2003; 3:359-371.

8. Araujo F, Slifer T, Li S, Kuver A, Fong L, Remington J. Gemifloxacin inhibits cytokine secretion by lipopolysaccharide stimulated human monocytes at the post‐transcriptional level. Clin Microbiol Infect 2004; 10:213-219.

9. Dalhoff A. Immunomodulatory activities of fluoroquinolones. Infection 2005; 33:55-70.

10. Sajid MS, Iqbal Z, Muhammad G, Sandhu MA, Khan MN, Saqib M, et al. Effect of ivermectin on the cellular and humoral immune responses of rabbits. Life Sci 2007; 80:1966-1970.

11. Thomas L, Asad M, Hrishikeshavan HJ, Chandrakala GK. Effect of centchroman on cellular and humoral immunity. Indian J Physiol Pharmacol 2007; 51:387-394.

12. Fulzele S, Satturwar P, Joshi S, Dorle A. Study of
the immunomodulatory activity of Haridradi ghrita in rats. Indian J Pharmacol 2003; 35:51-54.

13. Cho WCS, Leung KN. In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. J Ethnopharmacol 2007; 113:132-141.

14. Black CAP. Delayed type hypersensitivity: Current theories with a historic perspective. Dermatol Online J 1999; 5:7.

15. Fleming RA. An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy 1997; 17:146S-154S.

16. Winkelstein A. Mechanisms of immunosuppre-ssion: effects of cyclophosphamide on cellular immunity. Blood 1973; 41:273-284.

17. Shalit I, Kletter Y, Halperin D, Waldman D, Vasserman E, Nagler A, et al. Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G‐CSF in a murine model of cyclophospha mide‐ induced leukopenia†. Eur J Haematol 2001; 66:287-296.

18. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science 2010; 327:291-295.

19. Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nat Immunol 2004; 5:971-974.