Abstract

The study of health issues in captive and free ranging cetaceans has suggested reduced immune competence as well as opportunistic and chronic infectious diseases to be problematic. Understanding the basic function of the cetacean immune system is central to the study of cetacean health and illness, and cytokines are key mediators of a functioning immune system. To date there are few cetacean specific reagents available to test for immune function. There are, however, many mouse and human reagents readily available and a number of these, especially the cytokines, have been shown to possess interspecies cross reactivity.

Interleukin-2 (IL2) and interleukin-10 (IL10) are known to be important regulators of the immune system and modulators of the inflammatory process in both the human and the mouse. IL2 and IL10 are pleiotropic in activity, IL2 is thought to have general stimulatory effects on immune function while IL10 has been recognized for its important suppressive activities, especially in the development of cell mediated immunity and acute sepsis. In this study we have tested the human recombinant cytokines rhIL2, rhIL4 and rhIL10 for their ability to stimulate T cell proliferation (IL2 IL4) and inhibit cytokine synthesis by monocytes (IL10) in killer whale (Orcinus orca) peripheral blood.

The results show that killer whale peripheral blood mononuclear cells (PBMC) when stimulated with the mitogens ConA or PHA will proliferate in a dose dependent fashion to rhIL2, but not rhIL4 at levels comparable to a human control. In addition, killer whale PBMC will produce inflammatory cytokines, including interleukin-6 (IL6), when stimulated with the bacterial endotoxin lipopolysaccharide (LPS). The killer whale PBMC was stimulated with LPS in the presence or absence of rhIL10. The resultant supernatants were then assayed for IL6 like activity in a bioassay using the mouse cell line B9, which is dependent on IL6 for growth and has been shown to react with IL6 of many species. Our results show that killer whale IL6 production is inhibited by rhlL10 in a dose dependent fashion, and the specificity of this inhibition is demonstrated by including a neutralizing antibody to hIL10 which restores the IL6 production. These results indicate that certain recombinant human cytokines are able to function in a phylogenetically distant mammalian species. Human cytokines then have potential as reagents to test for immune functionality in exotic mammalian species, and could have diagnostic and therapeutic potential in cetaceans like they have in humans.