The effects of kainic acid-induced lesions in the lateral septal area on cell-mediated immune function.

The lateral septal area (LSA) is a primary control region for psychoneuroendocrine functions, and we have previously reported that kainic acid (KA) lesions in the LSA and the hippocampus have inhibitory and facilitatory effects, respectively, on the humoral immune response of female rats. Thus, these limbic structures may selectively participate in directing neuroimmune regulation. In order to assess the fundamental role of the LSA in neuroimmune regulation, we have evaluated the effects of neurotoxic septal lesions on various cell-mediated immune measures. Animals received stereotaxically guided bilateral infusions of KA (2.0 micrograms/microliter) or physiological saline (SHAM) into the LSA. Following a 2-week recovery period, animals were sacrificed and the spleen cells analyzed for natural killer (NK) cell activity and T-cell responsiveness to mitogen (ConA) or to anti T-cell receptor mAb (R73). A separate group of LSA-lesioned animals were immunized with sheep red blood cells 4 days prior to harvesting the spleen for plaque forming cell (PFC) number determination and measurement of TNF-alpha secretion from splenic macrophages. The results indicate that rats with KA lesions in the LSA have significantly higher NK cell activity, significantly lower numbers of splenic PFCs, and significantly reduced TNF-alpha secretion from splenic macrophages, relative to controls. There was a statistical tendency (p < .1) for reduced T-cell lymphoproliferative responses to ConA stimulation in LSA-lesioned animals, relative to SHAMs. However, the T-cell lymphoproliferative response to specific activation via the T-cell receptor was not significantly different between lesioned and control groups. These results further demonstrate the importance of KA-sensitive LSA neurons in neuroimmunoregulation. Moreover, selective alterations of different components of the immune system are observed in LSA-lesioned animals, suggesting that the LSA is involved in the complex and differential regulation of immunity.