Neuroendocrine immune features of pediatric inflammatory rheumatic diseases

Juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (JSLE) are the most common autoimmune rheumatic diseases in children associated with high levels of autoantibodies and immune reactivity. JRA and JSLE are more common in girls. Disease activity is worse in the morning, improves during the daytime and worsens at night suggesting that neuroendocrine immune mechanisms are involved in disease pathophysiology. Adult patients with RA and SLE have excessive levels of prolactin (PL) while cortisol (CS) production is down-regulated for the degree of ongoing inflammation. PL has potent proinflammatory properties. Normal to low levels of cortisol have been observed in children with active JRA despite the high serum levels of IL-6, IL-1 beta, and TNF-alpha, which activate the hypothalamic-pituitary-adrenal axis (HPA). The CS levels are in fact subnormal because inflammatory stress activates the HPA. Normal serum PL levels were seen in children with JRA, most of whom were not active with higher levels in those with active ANA +ve JRA complicated by uveitis. A trend toward high PL levels was seen in 33 children with JSLE. High serum PL levels are seen in patients with active juvenile ankylosing spondylitis (JAS) only. Growth retardation is a feature of JRA. Patients with JRA have low to normal levels of growth hormone (GH) and low levels of insulin-like growth factor 1 (IGF-1). IGF-1 mediates the effects of GH. The observation of low IGF-1 in JRA raises the therapeutic possibility with IGF-1. Overall, high levels of follicle stimulating hormone and luteinizing hormone are found in children with JSLE while the levels in JRA tend to be normal. Testosterone levels are low in patients with JRA. No significant differences in estrogen levels have been found between patients with JRA and those with JSLE and matched controls. There is evidence that the autonomic nervous function is defective in patients with JRA.