Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
(RA) is a chronic debilitating condition with a 2-3 fold greater prevalence in women
than men. Additionally, women have worse disease outcomes and a suspected increased
mortality. However, the etiology of sex differences in RA remains unclear. Tumor
necrosis factor-transgenic (TNF-Tg) mice, a model of inflammatory arthritis,
display similar sex differences as RA patients. To formally test the
hypothesis that female TNF-Tg mice have greater morbidity and mortality versus
male littermates, we assessed arthritic signs, function and time to death in a large
cohort of TNF-Tg mice and wild type (WT) controls.
mice (3647 line) and WT littermates (n=33) were monitored over six months, and
dates of death were recorded for Kaplan-Meier analysis. Grip strength, as an
indicator of arthritis, and weight was measured in male and female TNF-Tg mice
with active arthritis at five months of age. The same measurements were taken
in a cohort of mice at two months of age, prior to onset of clinical signs, and
four weeks later when frank arthritis was present.
shorter median lifespans than males (5.9 vs 8.1 months, p<0.05) (Fig. 1). Male
and female TNF-Tg mice have significantly decreased normalized grip-strength at
five months of age compared to WT sex-matched controls (0.05±0.001 vs 0.03±0.004
vs 0.10±0.01 vs 0.01±0.001, p<0.0001). At two months of age, female TNF-Tg
mice have decreased normalized grip-strength compared to age-matched male
TNF-Tg and female WT mice (0.079±0.01 vs 0.095±0.02 vs 0.10±0.01, p<0.05). Interestingly,
there was no clinical evidence of arthritis at this time. However, four weeks
later, tarsal joint swelling and an inability to splay digits was noted in hind
limbs of TNF-Tg mice, which was indistinguishable between sexes. Moreover, female
TNF-Tg displayed a significantly decreased rate of weight gain measured from two
months to three months of age compared to male TNF-Tg and female WT mice (1.01±1.71%
vs 7.11±1.18% vs 12.53±2.08%, p<0.001).
TNF-Tg female mice with chronic inflammatory arthritis have shorter lifespans
than male littermates. Grip-strength was decreased in female TNF-Tg earlier
than age-matched TNF males, indicating earlier onset of disease, although gross
signs of arthritis between sexes were not noted. Similarly, rate of growth as
measured by change in weight gain was decreased in female TNF-Tg mice at the
earliest manifestations of disease compared to male TNF-Tg mice. This is
similar to RA in which females are suggested to have increased morbidity and
mortality compared to males. Potential implications include sex hormone
interactions during TNF-mediated inflammation, raising the possibility that
modulating the hormonal environment could lessen the burden of RA in women.
Disclosure: R. Bell, None; R. Wood, None; J. Chakkalakal, None; C. T. Ritchlin, None; E. Schwarz, None; H. Rahimi, None.
To cite this abstract in AMA style:
Bell R, Wood R, Chakkalakal J, Ritchlin CT, Schwarz E, Rahimi H. Increased Morbidity and Mortality in Female Versus Male Tumor Necrosis Factor-Transgenic Mice [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/increased-morbidity-and-mortality-in-female-versus-male-tumor-necrosis-factor-transgenic-mice/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-morbidity-and-mortality-in-female-versus-male-tumor-necrosis-factor-transgenic-mice/