The Role of Substance P in Cytokine Production by Glial Cells

Substance P (SP), a neuropeptide released by peripheral sensory neurons, plays an important role in pain perception and acute inflammation (Sandberg and Iverson, 1982). It is also involved in peripheral autoimmune inflammatory diseases, most clearly with experimental adjuvant arthritis. Rats with adjuvant arthritis develop increased levels of SP in nerves innervating the arthritic joints, and depleting these animals of SP with capsaicin ameliorates the arthritis (Colpaert et al., 1983). Conversely, adding exogenous SP to the joint makes the arthritis more severe (Levine et al., 1984). Acute injury stimulates the release of SP (up to 2.8×10−15M into lymph) within 5–10 minutes (Jonsson et al., 1986). SP levels in blister fluid from infections, eczema, and bullous pemphigoid can be 3×10−11M (Wallengren et al., 1986), while SP in acute inflammatory exudates can be as much as 2×10−9M (Tissot et al., 1988), indicating high levels of SP secretion under these conditions. Inflammatory bowel disease tissue has a 1000-fold increase in SP receptors and is another instance where SP may be contributing to chronic inflammation (Mantyh et al., 1988).