9th multidisciplinary international

Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD

CONFERENCE ABSTRACTS 5. PSYCHONEUROIMMUNOLOGY

INTRANASAL ADMINISTRATION OF CYTOKINES IN BIOLOGICAL PSYCHIATRY

A.V. Kalueff

Medical School, University of Tampere, Tampere, Finland We have recently designed a protocol allowing to administer selected cytokines to the brain (Kalueff A.V., Lehtimaki K.A., Ylinen A., Honkaniemi J., Peltola J. Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats. Neurosci. Lett. 2004; 365(2): 106— 1 10) during experimental brain pathogenesis. In the abovementioned pioneering study, we analysed the role of a pleiotropic pro-inflammatory cytokine, interleukin-6 (IL-6), in epilepsy. Briefly, to examine this problem, we used human recombinant IL-6 applied intranasally (400 ng/40 microl) to rats 1h before seizures induced by systemic injection of pentylenenetrazole (PTZ, 75 mg/kg). Intranasal administration was performed by fixing an animal in a vertical position head up is a special fixing device for 5 min, and slow infusion of cytokines manually by a 50-mkl micropipette. This method allows to infuse cytokines in normal awake animals, thus avoiding surgery or the use of anesthetics — both representing unwanted additional factors in the experimental brain research. Overall, compared to the saline-treated control animals (n = 11 in each group), IL-6-treated rats demonstrated elevated levels of IL-6 in the frontal lobe (measured by ELISA) and increased severity of PTZ-induced seizures (shorter latency, longer duration and higher mortality). Our findings, using epilepsy as a model of brain pathology, showed that exogenous IL-6 plays a pro-convulsant role in the brain and suggest that the IL-6 system may be a novel target for the development of anticonvulsant drugs (Kalueff et al., 2004). Our subsequent preliminary studies have also shown that similar approach may be used for some other cytokines, e.g. IL1-Ra (40—80 mkl, i.n.). Collectively, these data suggest that intranasal administration of cytokines, following our protocol, may allow them to bypass the blood-brain barrier and reach the brain in a specific way not requiring the use of anesthetic drugs. Our data are consistent with several other recent findings (Frey et al., 2000—2004) showing that intranasal transport of relatively big molecules such as cytokines, may reach the brain within a relatively short time (e.g., 20—40 min). In general, this method enables specific targeting the brain and selected brain-neuroimmune mechanisms using intranasal administration. In this presentation, we will review and discuss in detail potential applications of our method in biological psychiatry, with a special focus on its utility for psychoneuroimmunology.

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 911

Psyhopharmacology & biological narcology

ISSN 1606-8181