Neurocysticercosis, caused by the cestode Taenia solium, is the most common
parasitic infection of the human central nervous system that leads to
seizures. Taenia crassiceps
cysticercosis in mice is an experimental model for
Taenia solium cysticercosis. Similar to the human
infection, live parasites cause little or no granulomatous
inflammation. Dying parasites initiate a granulomatous reaction. The
neuropeptide,
substance P (SP), stimulates T-helper (TH) 1
cytokine production. In the current studies, we determined whether absence of SP/SP receptor circuitry in the SP-precursor,
preprotachykinin, knockout or SP-receptor, neurokinin (NK) 1, knockout mice affected
granuloma cytokine production. We hence compared the levels of Th1
cytokines interleukin (IL)-2 and
interferon (IFN)-gamma, and levels of Th2/immunoregulatory
cytokines IL-4 and
IL-10, by
enzyme-linked
immunosorbent assay in T. crassiceps-induced
granulomas derived from infected C57BL/6 wild type (WT) versus SP-precursor knockout and NK1 knockout mice. We found that mean levels of
IL-2, IFN-gamma,
IL-4, and
IL-10 in infected WT-derived
granulomas were significantly higher than those of
granulomas derived from infected SP-precursor knockout or the NK1 receptor (NKIR)knockout mice. Levels of Th2/immunoregulatory
cytokines,
IL-4 and
IL-10 were higher in early stage
granulomas (histologically-staged on basis of evidence of parasite remnants) versus late stage
granulomas (no parasite-remnants) of both knockouts, whereas the reverse was noted in WT-derived
granulomas. These study established that the absence of an SP/SP receptor circuitry in the SP precursor knockout mice or NK1 receptor knockout mice led to an inhibited
cytokine response.