Poster Presenter

Cytokine Profiles after Somatostatin Drug Delivery in Schistosoma mansoni Infected Rodents
Shyama Chatterjee, Thomas Panis, Amit Bernat, Chris Bridts, Wim Stevens, Eric Van Marck

Objectives: Our previous work has demonstrated an association between liver fibrosis and low endogenous levels of the neuropeptide somatostatin in S. mansoni infected Senegalese subjects (1). Experiments have revealed an antifibrotic effect of somatostatin therapy on S. mansoni infected outbred mice, suggesting that exogenous somatostatin may reduce the secretion of fibrosis probably by decreasing inducing-mediators (2), including IFN-gamma (3).

This study investigated whether somatostatin therapy modulates cytokine expression in S. mansoni infected, inbred mice strains - C57BL6 (develop light pathology via balanced T1/T2 immune reactions) and the C3H mice (infection triggers serious pathology via strong T1 and T2 responses).

Methods: Somatostatin (Somatostatin-UCB®) therapy (90 μg/day for 2/5 days) was given to S. mansoni infected inbred mice. Biochemical assessment of fibrosis was done by the hydroxyproline protocol (4). Radioimmunoassay (Gut Hormone lab. KUL, Leuven), was used to study the evolution of inherent somatostatin levels in mice strains. A week after somatostatin therapy, mice spleens were extracted, cells stimulated in culture with Con A, and a Cytometric Bead Array (R&D) kit was used to screen for levels of IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-5 in the culture supernatants.

Results: In outbred Swiss and inbred C3H mice, S. mansoni infection increased endogenous somatostatin levels in the acute stage (8 weeks) of infection, whereas levels were reduced in chronic stages (16 weeks) (P=0.01). In the low pathology C57BL6 mice, the reverse trend was noticed. In infected C57BL6 mice, somatostatin therapy provided no relief from S. mansoni caused pathology. In contrast, a marked modulation of fibrosis was noted in infected C3H mice strain. Here, somatostatin treatment caused a significant decrease in hydroxyproline levels at wk 8 (2.03 ± 0.16 μmol) and at wk16 (2.88 ± 0.18 μmol) (P<0.0001), when compared to the respective values in untreated animals. Splenic T cells isol ated from somatostatin treated, C3H mice, 8 weeks infected, were stimulated by Con A to secrete IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5. The levels were comparable to that obtained from T cells from untreated animals. However at 16 weeks of infection, somatostatin therapy caused a significant decrease in IFN-gamma and IL-2 levels secreted by splenic T cells from C3H mice. No significant variations were observed in the levels of the other cytokines studied.

Conclusion: The anti-inflammatory effects of somatostatin may occur via a selective inhibitory effect on IFN-gamma production in infected C3H mice.

References
1&2. Chatterjee et al. (2004); (2005).
3. Weinstock & Elliott (1990). 4. Bergman and Loxley (1963).