Serum zinc and copper in active rheumatoid arthritis: Correlation with interleukin 1? and tumour necrosis factor ?

Abstract

Serum zinc and copper levels and serum interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) levels were evaluated in 57 female patients with active rheumatoid arthritis (RA) to investigate a possible role of IL1 beta and TNF alpha on zinc and copper homeostasis in RA. Serum zinc levels were significantly lower and serum copper levels significantly higher in RA patients when compared with osteoarthritis or asymmetrical psoriatic oligoarthritis patients and with normal controls. No differences were observed in serum IgM rheumatoid factor positive and serum IgM rheumatoid factor negative patients as regards serum zinc and copper concentration. In RA patients the erythrocyte sedimentation rate and acute-phase proteins correlated negatively with serum zinc and positively with serum copper. IL1 beta and TNF alpha were found to correlate negatively with zinc and positively with copper in RA patients. Lower levels of zinc may be due to an accumulation of zinc-containing proteins in the liver and in the inflamed joints in RA. Elevated serum copper levels seem to be linked to the increased synthesis of ceruloplasmin by the liver.

Differential Gene Expression after Zinc Supplementation and Deprivation in Human Leukocyte Subsets

“…One major group of genes affected by zinc status is related to inflammation, and zinc can directly affect several kinds of inflammatory diseases, including rheumatoid arthritis, diabetes, asthma, and sepsis (6)(7)(8)(9)(10)(12)(13)(14). Another interesting aspect of zinc status is found in elderly individuals, who in general show a significant reduction of their plasma or serum zinc levels.…”

“…Zinc deficiency occurs as a result of malnutrition, aging, and inborn or acquired impairment of zinc uptake, and can lead to thymic atrophy, malfunction of immune cells, and subsequently, high incidence of infections (5). In addition, several diseases with immunological etiologies, including inflammation, rheumatoid arthritis, diabetes, and asthma, are accompanied by zinc deficiency (6)(7)(8). Many studies indicate that pharmacological zinc supplementation can be beneficial.…”

“…In nonobese diabetic mice, an animal model for type I diabetes, the incidence of spontaneously occurring diabetes was reduced by zinc supplementation (9). Zinc supplementation has been shown to have beneficial effects in rheumatoid arthritis (10), and the negative correlation between serum zinc and pro-inflammatory cytokine levels in rheumatoid arthritis indicates a link between zinc and the severity of the disease (6). In elderly people, who have a particularly high risk of zinc deficiency, zinc supplementation improves responsiveness to immunization, serum thymulin activity, delayed type hypersensitivity reactions, and T-cell proliferation in response to mitogens (11).…”

Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis

“…Ninety percent of the serum copper is incorporated to the ceruloplasmin (Rosenstein & Caldwell, 1999), which is one of the main extracellular antioxidants (Kiziltunc et al, 1998). Therefore, the increase of serum copper may be due to the increase of the ceruloplasmin, which is an acute phase protein (Conforti et al, 1983), whose role in adjuvant arthritis is to neutralize free oxygen radicals, mainly anion superoxide (Zoli et al, 1998) in an attempt to stop the process of turning chronic.…”

“…Thus, the significant correlation between serum decrease and hepatocyte increase may signify that this increase occurs at serum depletion cost (Oliva et al, 1987;Zoli et al, 1998). Serum albumin, which is an important Zn-carrier, is decreased during inflammation, and presents positive correlation with the reduced zinc levels (Milanino et al, 1993;Maes et al, 1997).…”