Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat

Abstract

Both severe and marginal copper deficiency were produced in male Sprague Dawley rats prior to induction of adjuvant arthritis. Degree of copper deficiency was confirmed by analysis of plasma, liver, and brain samples prior to adjuvant injection. Incidence of adjuvant arthritis was the same in both copper deficient and control animals although the severity was slightly but not statistically less in the former. However, recovery from foot edema was impaired in copper-deficient animals, while marginally copper-deficient animals recovered at the same rate as did controls. Plasma copper concentration increased in response to the injection of adjuvant and the increase was directly related to dietary copper content. Plasma zinc concentration was decreased in arthritic animals and the decrease was inversely correlated to paw edema. Liver copper, zinc, and iron concentrations in arthritic animals remained unchanged or increased slightly in comparison to the corresponding non-injected controls. Copper-deficient rats were immunosuppressed as demonstrated by impaired responsiveness to the T-cell dependent contact sensitizing agent oxazolone and diminished capacity to respond to the T-cell independent antigen Type III pneumococcal polysaccharide. Although a statistical difference in paw volumes was not found for group of animals fed diets differing in copper content, it is postulated that copper deficiency may alter the severity and kinetics of adjuvant arthritis by impairing aspects of the immune response and the tissue repair processes subsequent to injury.

Review: Copper and inflammation — a possible rationale for the pharmalogical manipulation of inflammatory discorders

“…Some attempts have been made to clarify whether liver copper stores are directly involved in the changes of copper metabolism that occur during chronic inflammation. Thus KARABELAS found a dramatic increase of liver copper concentration (+180%) 21 days after the injection of Mycobacterium tubercolosis suspended in paraffin oil in the rat [30], and KISHORV et al found a modest increase of liver copper concentration (+30%) under similar experimental conditions [15]. By contrast, FELDMAN and co-workers reported an over 50% decrease of liver copper concentration in the dog following the subcutaneous injection of,, complete Freund's adjuvant [32].…”

“…Nevertheless, KISHORE and co-workers did not find any inhibition in the development of the polyarthritic syndrome. The percentage of rats who developed the experimental disease was the same in both copperdeficient and control animals, although the severity of limb swelling was slightly but not statistically less in the former; moreover, the recovery from foot oedema was impaired in copper-deficient animals but not in the marginally copper-deficient rats who recovered at the same rate as did controls [15].…”

“…Recently, KISHORE et al [15] designed experiments aimed also to determine if the reduction in inflammation previously observed in adjuvant-challenged copper-deficient animals was an epiphenomenon of the immune system, i.e. an event secondary to an impairment of the immune function of the young rat.…”

Copper and zinc status during acute inflammation: studies on blood, liver and kidneys metal levels in normal and inflamed rats

“…A likewise complex situation is found looking at the data reporting liver zinc concentration values measured in different experimental animals and pathologies. Indeed the metal concentration in liver rised in rat with endotoxemia and Francisiella tulariensis infection [12], and adjuvant arthritis [13], but it was found to be significantly decreased in the dog injected with complete Freund's adjuvant [20]. In our opinion, the above data clearly shown that the understanding of copper and zinc metabolism during inflammation is still inadequate and it merits improvement especially to obtain valuable indications of the convenience of spending more effort in studying the pharmacological manipulation of these metals as a new approach to the therapy of inflammation disorders.…”

“…Nevertheless this can not be taken as a general rule. For example serum (or plasma) zinc was found to be decreased in rat with turpentine abscesses [11], endotoxemia and Francisiella tulariensis infection [12], adjuvant arthritis [13], and in man experimentally infected with sandly fever virus [14] or affected by active rheumatoid arthritis [15,16]. Conversely the injection of complete Freund's adjuvant in the dog [17] caused an increase in serum zinc concentrations, and similar data were reported studying mixed connective tissue disease in man [16].…”