Immunomodulatory Activity of the Marine Sponge, Haliclona (Soestella) sp. (Haplosclerida: Chalinidae), from Sri Lanka in Wistar Albino Rats: Immunosuppression and Th1-Skewed Cytokine Response

Abstract

Natural secondary metabolites of sponges of the genus Haliclona are associated with an array of biological activity with therapeutic usage. We investigated the immunopharmacological properties of a presumably novel marine sponge species from Sri Lanka, Haliclona (Soestella) sp. Sponge material was collected from southern Sri Lanka by scuba diving. Sponge identification was based on spicule and skeleton morphology using light microscopy. Selected in vivo and ex vivo tests investigated nonfunctional and functional immunomodulatory activity of the Haliclona (Soestella) sp. crude extract (HSCE) in the Wistar rat model. Compared to the controls, rats orally gavaged daily for 14 consecutive days with 15 mg/kg dose of the HSCE manifested a significant reduction of immune cell counts of total WBCs (by 17%; $p<0.01$ ), lymphocytes (38%), platelets (52%), splenocytes (20%), and bone marrow cells (BMC; 60%) ( $p<0.001$ ), with a concurrent increase in the neutrophil : lymphocyte ratio ( $p<0.05$ ); RBC counts abated by 53% ( $p<0.001$ ). A significant reduction of the splenosomatic index was evident with the 10 and 15 mg/kg doses ( $p<0.001$ ). Rat plasma TNF-α cytokine level was augmented by tenfold ( $p<0.001$ ), IL-6 level by twofold ( $p<0.01$ ) with the 15 mg/kg HSCE treatment, while IL-10 was detectable in rat plasma only with this treatment; the corresponding Th1 : Th2 cytokine ratio (TNF-α : IL-10) was indicative of an unequivocal Th1-skewed cytokine response ( $p<0.01$ ). Ex vivo bone marrow cell and splenocyte proliferation were significantly and dose dependently impaired by HSCE ( $\text{I}{\text{C}}_{50}$ 0.719 and 0.931 μg/mL, respectively; $p<0.05$ ). Subacute toxicity testing established that HSCE was devoid of general toxic, hepatotoxic, and nephrotoxic effects. In conclusion, HSCE was orally active, nontoxic, and effectively suppressed nonfunctional and functional immunological parameters of Wistar rats, suggestive of the potential use of the HSCE as an immunosuppressant drug lead.