title: Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy.
abstract: Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of epilepsy worldwide. Larval degeneration, which may follow antiparasitic treatment, results in clinical symptoms due to inflammatory cell influx. Mechanisms regulating this are not well understood, but chemokines have a key role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags. Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited by anti-IL-10 Abs. Plasma CXCL8, TNF-α, IL-10, eotaxin, IL-1, IL-1ra, soluble IL-1R-II, and soluble TNFR-I and -II levels were evaluated in 167 NCC patients. Patients had lower plasma CXCL8 and TNF-α concentrations than control subjects. In summary, larval Ags from brain and muscle cysts differentially regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is decreased, leading to inflammatory cell influx. Taken together, the cellular, porcine, and human data may explain, in part, why NCC is usually asymptomatic but may cause proinflammatory symptoms, particularly following treatment.
authors.affiliation: Department of Infectious Diseases and Immunity, Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College London, London, United Kingdom.
authors.forename: Jasim
authors.initials: J
authors.lastname: Uddin
authors.forename: Armando E
authors.initials: AE
authors.lastname: Gonzalez
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Lynette H
authors.initials: LH
authors.lastname: Thomas
authors.forename: Silvia
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Carlton A W
authors.initials: CA
authors.lastname: Evans
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
authors.forename: Hector H
authors.initials: HH
authors.lastname: Garcia
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
mesh_terms: D000818:Animals; D000947:Antigens, Helminth; D000977:Antiparasitic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D003560:Cysts / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020019:Neurocysticercosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D013552:Swine
chemical_list: D000947:Antigens, Helminth; D000977:Antiparasitic Agents; D018925:Chemokines; D016209:Interleukin-8
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