title: Anti-inflammatory and immunomodulatory effect of an extract of Coccidioides posadasii in experimental arthritis.
abstract: Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1β, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.
authors: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors: Ana Carolina Matias Dinelly
authors: AC
authors: Pinto
authors: Rossana de Aguiar
authors: Rde A
authors: Cordeiro
authors: José Julio Costa
authors: JJ
authors: Sidrim
authors: Ana Karine Rocha de Melo
authors: AK
authors: Leite
authors: Ana Caroline Rocha de Melo
authors: AC
authors: Leite
authors: Virgínia Cláudia Carneiro
authors: VC
authors: Girão
authors: Raimunda Sâmia Nogueira
authors: RS
authors: Brilhante
authors: Marcos Fábio Gadelha
authors: MF
authors: Rocha
authors: Fernando de Queiroz
authors: Fde Q
authors: Cunha
authors: Francisco Airton Castro
authors: FA
authors: Rocha
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D001168:Arthritis / Q000188:drug therapy* / Q000473:pathology; D001688:Biological Products / Q000008:administration & dosage* / Q000302:isolation & purification; D002061:Bursa, Synovial / Q000473:pathology; D003045:Coccidioides / Q000737:chemistry*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000008:administration & dosage / Q000302:isolation & purification; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000302:isolation & purification; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D016207:Cytokines; D005656:Fungal Proteins; D007155:Immunologic Factors
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