Effect of Colchicine on Inducible Nitric Oxide Synthase Activity and Nitric Oxide Production of Mice Induced by &amp;lt;i&amp;gt;Aggregatibacter actinomycetemcomitans&amp;lt;/i&amp;gt;

Wihaskoro Sosroseno,Phillip S Bird,Endang Herminajeng

doi:10.4236/jbm.2019.712003

Abstract

Objective: Colchicine induced a non-protective Th2-like immunity in Aggregatibacter actinomycetemcomitans-stimulated murine immune response. The aim of the present study was to determine whether colchicine affects inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production in A. actinomycetemcomitans-immunized mice. Materials and Methods: BALB/c mice were sham-immunized (group I) or immunized with heat-killed A. actinomycetemcomitans (group II-VII). Colchicine was injected intraperitoneally before (group III), on the same day of (group IV), or after (group V) the primary immunization and on the same day of (group VI) or after (group VII) the secondary immunization. In vitro, spleen cells from either sham- or heat-killed A. actinomycetemcomitan-immunized animals were cultured and stimulated with heat-killed A. actinomycetemcomitans in the presence or absence of colchicine with or without addition of L-arginine, Db-cAMP, forskolin or interferon-γ (IFN-γ). The levels of splenic iNOS activity and both serum and culture supernatant NO levels were assessed. Results: The results showed that colchicine did inhibit both splenic iNOS activity and serum NO levels only when the drug was injected at the same time as the immunization (group IV and VI). Splenic iNOS activity and NO levels on antigen-stimulated spleen cell cultures were also suppressed by colchicine, even in the presence of L-arginine, Db-AMP or forskolin. IFN-γ only partially restored iNOS activity and NO levels in the antigen and colchicine-treated spleen cell cultures. Conclusion: This study suggests, therefore, that colchicine may suppress the iNOS activity and NO production in A. actinomycetemcomitans-immunized mice in vivo and in vitro.

Highlights

Colchicine, an alkaloid extract from Colchicum, is used to treat a diverse number of inflammatory conditions, such as Behçet’s disease, acute gout, familial Mediterranean fever (FMF), pericarditis and other cardiovascular disorders [1]
When heat-killed A. actinomycetemcomitans-stimulated cell cultures treated with dibutyryl cyclic adenosine monophosphate (Db-cAMP) or forskolin, both inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production were significantly increased as compared with the antigen-stimulated cell cultures (p < 0.05) (Figure 4)
The results showed that the levels of both INOS activity and NO production by heat-killed A. actinomycetemcomitans-stimulated cell cultures in the presence of both colchicine and IFN-γ were lower than those in the presence of IFN-γ alone but much higher than those in the presence of colchicine alone (p < 0.05) (Figure 5), suggesting that IFN-γ may partially abrogate the suppressive effect of colchicine on iNOS activity and NO production of antigen-stimulated cell cultures

Summary

Introduction

Colchicine, an alkaloid extract from Colchicum (autumn crocus), is used to treat a diverse number of inflammatory conditions, such as Behçet’s disease, acute gout, familial Mediterranean fever (FMF), pericarditis and other cardiovascular disorders [1] This drug enhanced both antibody production [2] [3] and dendritic cell functions [4], but inhibited monocyte and polymorphonuclear cell migration [5] [6] and cell-mediated immunity [7]. The additional of colchicine in the cultures of spleen cells isolated from heat-killed A. actinomycetemcomitans immunized-immunized mice resulted in increased splenic-specific IgG1, IL-4 and cell proliferation but suppressed specific IgG2a and IFN-γ levels [30] This suggested that colchicine may stimulate a T-helper 2 (Th2)-like immunity specific to A. actinomycetemcomitans in vitro [30].

Methods

Results

Discussion

Conclusion