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.