Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by persistent inflammation, joint destruction, and notable differences in prevalence and severity between sexes. Elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumour necrosis factor alpha (TNF-α), are well established mediators of RA pathology. Although extensive research has elucidated their pathological roles, the influence of sex on cytokine profiles and RA outcomes remains undefined.
This review examines preclinical and clinical studies analysing sex-specific cytokine responses in RA. Findings reveal that female patients and experimental models exhibit higher concentrations of pro-inflammatory mediators, with oestrogen and androgen signalling playing relevant roles in modulating cytokine expression and disease severity. Ovariectomised female rodents and postmenopausal RA patients display elevated IL-1 and IL-6 levels which are associated with more severe inflammatory disease. In contrast, testosterone or oestrogen replacement reduced cytokine production and inflammatory burden. However, the effects of oestrogen on RA inflammation appear contradictory, likely reflecting differences between endogenous hormonal fluctuations and exogenous or experimental exposure, as well as context-dependent immune responses inadequately represented in preclinical models. Genetic and immunological studies further implicate enhanced IL-6 signalling as a female-specific risk factor for RA, alongside increased IRF5 positive B cells and heightened TLR9 mediated TNF-α production.
Overall, this review highlights pronounced sex-dependent differences in cytokine driven inflammation underlying RA pathogenesis and supports the integration of sex-informed research frameworks and integrative analytical approaches to improve RA research and outcomes.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Bartley, Ella Margaret Miss
(2026)
"Sex Differences And Cytokine Profiles In Rheumatoid Arthritis,"
International Undergraduate Journal of Health Sciences: Vol. 6:
Iss.
1, Article 2.
DOI: https://doi.org/10.61862/2811-5937.1100
Available at:
https://sword.mtu.ie/iujhs/vol6/iss1/2
Full Publication Date
7-30-2026
Publisher
Munster Technological University
Resource Type
review
Access Rights
open access
