Sublingual immunotherapy alters expression of IL‐4 and its soluble and membrane‐bound receptors

Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL‐4, and its soluble and membrane‐bound receptor in patients with SAR before and after SIT. Using allergen‐challenge assays, we found that SIT treatment decreased IL‐4 cytokine levels, as previously reported. We also observed a significant decrease in the IL‐4 membrane‐bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL‐4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.     

Interleukin‐17‐ and interleukin‐22‐secreting myelin‐specific CD4+ T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients

Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)‐specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS‐derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin‐6 (IL‐6), granulocyte–macrophage colony‐stimulating factor, IL‐17 and IL‐22 was less sensitive to hydrocortisone inhibition, only IL‐17 and IL‐22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL‐17 and IL‐22 production by MBP‐specific CD4⁺ T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL‐17‐ and IL‐22‐secreting CD4⁺ T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis.     

Significance of the role of self‐study and group discussion

The study of anatomy is experiencing a reduction in course duration and content, lecture and dissection hours, and number of lectures and examinations. This necessitates that medical students develop skills for self‐study. Toward that end, a self‐study module in basic anatomy was tested. Fifty‐seven new entrants were given a pretest (Pretest A) containing a questionnaire on basic anatomy. Then, in three groups each of 11 and two groups each of 12, they learned basic anatomy from recommended books in the library by self‐study for 2 hours. They discussed what they had learned among their group members during a practical exercise, followed by a posttest (Posttest A). A control group of 57 new entrants during another year was given the same pretest (Pretest B) and a lecture on basic anatomy. Then, without opportunity for self‐study, they were given a posttest (Posttest B). The answers were scored out of 40. The students' mean mark in Pretest A was poor. All the groups performed well in the practical exercise. In Posttest A, the mean mark increased significantly (P < 0.001), by 9.4. It shows that self‐study and group discussions significantly helped the students in construction of core anatomical knowledge as well as the acquisition, assimilation, and application of anatomical concepts and content. The mean mark in Pretest B was also poor. In Posttest B, the mean mark increased significantly (P < 0.001), by 14.2. This indicates that the traditional teaching session is also useful and serves to advance student knowledge. Thus our innovative study module can create a positive learning environment and can become an alternative to traditional instruction in teaching anatomical terminology and basic anatomy. Clin. Anat. 12:277–280, 1999. © 1999 Wiley‐Liss, Inc.     

Eosinophil‐derived cytokines in health and disease: unraveling novel mechanisms of selective secretion

Over the past two decades, our understanding of eosinophils has evolved from that of categorically destructive effector cells to include active participation in immune modulation, tissue repair processes, and normal organ development, in both health and disease. At the core of their newly appreciated functions is the capacity of eosinophils to synthesize, store within intracellular granules, and very rapidly secrete a highly diverse repertoire of cytokines. Mechanisms governing the selective secretion of preformed cytokines from eosinophils are attractive therapeutic targets and may well be more broadly applicable to other immune cells. Here, we discuss recent advances in deciphering pathways of cytokine secretion, both from intact eosinophils and from tissue‐deposited cell‐free eosinophil granules, extruded from eosinophils undergoing a lytic cell death.