ABSTRACT
Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 µg/5 µL per joint), isotype control (rat IgG 10 µg/5 µL per joint) or PBS (5 µl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA.
Subject(s)
Antibodies, Monoclonal/pharmacology , Arthritis, Experimental/physiopathology , Knee Joint/physiopathology , Pain/physiopathology , Receptor, Macrophage Colony-Stimulating Factor/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Arthritis, Experimental/drug therapy , Arthritis, Experimental/immunology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/physiopathology , Edema/drug therapy , Edema/pathology , Freund's Adjuvant , Inflammation/immunology , Injections, Intra-Articular , Knee Joint/immunology , Knee Joint/pathology , Male , Mice, Inbred ICR , Pain/drug therapyABSTRACT
A study of breast cancer survival was conducted among New Mexico Hispanic and non-Hispanic white women and New Mexico and Arizona American Indian women diagnosed between 1973 and 1992. The goals were to determine whether, after adjusting for first treatment and the extent of disease at diagnosis, American Indian and Hispanic women had poorer survival than non-Hispanic whites and, if survival had improved over time, whether comparable improvements had been made for the three racial/ethnic groups. Five-year relative survival rates were calculated, and a Cox proportional hazards model was constructed to compare survival between races/ethnicities, adjusting for first treatment and the extent of disease at diagnosis. Findings indicate that during 1983-1992, breast cancer was more commonly detected at a local stage for all three groups compared to 1973-1982. Five-year relative survival improved for non-Hispanic white and American Indian women with local or regional disease, but the improvement was statistically significant only for non-Hispanic white women and for American Indian women with local disease. Despite earlier stages at diagnosis, Hispanic females showed less improvement in overall or stage-specific survival than non-Hispanic whites. The Cox model indicated that American Indian women experienced poorer survival than non-Hispanic whites during both time periods. Survival of Hispanic women with breast cancer was comparable to non-Hispanic whites during 1973-1982 but was significantly worse during 1983-1992. The significance of this lower survival is amplified by increasing breast cancer incidence among New Mexico Hispanics and American Indians.