Divergent Effects of Endogenous and Exogenous Glucocorticoid‐Induced Leucine Zipper in Animal Models of Inflammation and Arthritis

Objective

Glucocorticoid‐induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency would exacerbate experimental immune‐mediated inflammation and impair the effects of glucocorticoids on inflammation and, correspondingly, that exogenous GILZ would inhibit these events.

Methods

GILZ^−/− mice were generated using the Cre/loxP system, and responses were studied in delayed‐type hypersensitivity (DTH), antigen‐induced arthritis (AIA), K/BxN serum–transfer arthritis, and lipopolysaccharide (LPS)–induced cytokinemia. Therapeutic expression of GILZ via administration of recombinant adeno‐associated virus expressing the GILZ gene (GILZ‐rAAV) was compared to the effects of glucocorticoid in collagen‐induced arthritis (CIA).

Results

Increased T cell proliferation and DTH were observed in GILZ^−/− mice, but neither AIA nor K/BxN serum–transfer arthritis was affected, and GILZ deficiency did not affect LPS‐induced cytokinemia. Deletion of GILZ did not impair the effects of exogenous glucocorticoids on CIA or cytokinemia. In contrast, overexpression of GILZ in joints significantly inhibited CIA, with an effect similar to that of dexamethasone.

Conclusion

Despite effects on T cell activation, GILZ deficiency had no effect on effector pathways of arthritis and was unexpectedly redundant with effects of glucocorticoids. These findings do not support the hypothesis that GILZ is central to the actions of glucocorticoids, but the efficacy of exogenous GILZ in CIA suggests that further evaluation of GILZ in inflammatory disease is required.

     

The epidemiology of pneumococcal carriage and infections in Malaysia

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.     

Status Dystonicus in a Child with Familial Idiopathic Hypoparathyroidism

Hypoparathyroidism leading to status dystonicus is rarely reported in literature. The authors present an 8-y-old girl with idiopathic familial hypoparathyroidism who presented with status dystonicus. She was managed successfully with midazolam infusion, calcium and vitamin D supplementation, and oral anti-dystonia drugs.