IL-1β as an important mediator of macrophage-chondrocyte crosstalk in pararamosis (rainforest arthritis).

BACKGROUND: Pararamosis, or pararama-associated phalangeal periarthritis, is a neglected tropical disease affecting rubber tappers in the Amazon, caused by contact with the urticating bristles of the Premolis semirufa caterpillar. This condition leads to chronic synovitis and progressive cartilage degradation, key features shared with other osteoarticular conditions such as osteoarthritis. METHODS: We investigated the inflammatory mechanisms of pararamosis by examining macrophage polarization and the subsequent crosstalk with chondrocytes. THP-1-derived macrophages were treated with P. semirufa bristles extract (PsE) to assess polarization and inflammasome activation. Furthermore, we compared inflammatory and catabolic markers in chondrocyte monocultures versus macrophage-chondrocyte co-cultures. RESULTS: PsE stimulation induced a robust M1 macrophage phenotype, evidenced by the upregulation of CD80, CD86, and TLR2, alongside increased expression of inflammasome components (NLRP3 and CASP1) and pro-inflammatory cytokines (IL1B, IL6, IL8, IL23A, and IL33). These transcriptional changes were accompanied by increased IL-1β, IL-6, and TNF-α secretion, confirming the pro-inflammatory phenotype. While PsE directly induced chondrocytes to express matrix metalloproteinases (MMPs) and inflammatory cytokines, these effects were significantly amplified in co-culture. The macrophage-chondrocyte interaction exacerbated the secretion of IL-6, IL-11, IL-23, CCL2, CCL5, MMP-1, MMP-3, and MMP-13. Crucially, antibody-mediated neutralization of IL-1β in co-cultures significantly attenuated the production of IL-11, IL-23, MMP-1, and MMP-3, while other pathways likely contribute to the regulation of additional inflammatory mediators. CONCLUSION: Our findings demonstrate that PsE promotes a sustained pro-inflammatory macrophage response and establishes a pathogenic crosstalk between macrophages and chondrocytes that amplifies inflammatory and catabolic signaling. The data identify IL-1β as a major regulator of this interaction and support the involvement of inflammasome-related pathways in the response to PsE. These results advance our understanding of the mechanisms underlying pararamosis and reveal biological features shared with osteoarthritis, providing a foundation for future studies aimed at validating the role of IL-1β and other inflammatory mediators in vivo.