Inhibitory effects of calcitonin gene-related peptide (CGRP) on murine retroviral infection of glial cells (168.34)

Abstract We have observed that C57BL/6 (B6) mice infected with a murine retroviral isolate, LP-BM5 developed peripheral neuropathy, along with an elevated expression of calcitonin gene-related peptide (CGRP), in addition to glial activation in the spinal cord. To investigate how these spinal cord changes might contribute to the development of peripheral neuropathy, we examined the effects of CGRP on LP-BM5-induced glial cytokine responses in vitro. Mixed spinal cord glia were prepared from adult B6 mice and infected with various doses of LP-BM5 (0, 1, 10, 100, and 1000 pfu/ml), with or without CGRP co-treatment (1ug/ml). Resulting levels of selected cytokines (IL-1β, IL-6, TNFα, IFNγ, IL-12, and CCL2) in the culture supernatants were measured 1, 4, and 7 days post-treatment via ELISA. Viral loads in both the cells and supernatants were determined at day 7 post-treatment using plaque assay. While little virus was detected in the supernatants, CGRP treatment appeared to reduce viral loads in the infected glial cells. This reduction was correlated with the decrease of LP-BM5 induced TNFα production. IL-6 and CCL2 production, however, were enhanced by CGRP treatment. Further, CGRP did not affect the levels of IL-12p40, and IL-1β, IFNγ. IL-12p70 was not detectable following any treatment. Altogether, the neuropeptide CGRP appears to inhibit viral infection of glial cells. Further study will help to understand the role of CGRP during retroviral infection-induced neurological defects.