This review examines recent articles on the relationship of cytokines to allergy and inflammation with particular emphasis on interleukin (IL)-4. The objective of this article is therefore to review published studies to identify cytokines consistently involved in allergic inflammation. Proinflammatory cytokines, including IL-4, IL-5, IL-13 and GM-CSF along with TNF-alpha play a role in allergen-induced airway leukocyte recruitment and these cytokines can be generated by T mast cells and other cells. In addition, IL-9, IL-25, IL-33, IL-17, IL-27 and IFN-γ are deeply involved in the regulation of asthma. Blocking the effect of these proinflammatory cytokines might provide new therapeutic approaches for the control of allergy and inflammation.

No abstract

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFκB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Cytokine is a term used for a large group of proteins that are produced by a variety of cells in the body and act to stimulate, or inhibit, the functions of the same cells that produce them (autocrime) or of other cell types (paracrime) (1-29). Interleukin-17 (IL-17), now known as IL-17 A, was originally cloned from T cell hybridoma and has been characterized as a proinflammatory cytokine produced by CD4+ CD4?RO+ memory T cells. According to the human genome sequencing and proteomics, five additional members, IL-17B, IL-l7C, IL-17D, IL-17Ea,ndIL-17F, have been identified and cloned. Some cognate receptors for the IL-17 family have been identified as IL-17R, IL-17RH 1, IL-17RL (receptor like), IL-17RD and IL-17RE(30-31). Altough it is believed that IL-17 is released by Th 1 or ThO cells but not by Th2 cells(32), It is interesting that there are some report demonstrated that TH2 CD4+ cell clone from patients with nickelallergic contact dermatitis also released IL-17 (33). The IL-17 family members are different in expressions and proinflammatory responses. IL-l7B mRNA is expressed at very high levels in the spinal cord and at lower and variable levels in the trachea, prostate, lung, small intestine, testes, adrenal, and pancreas. In situ analysis of mouse spinal cord, dorsal root ganglia, and brain demonstrated that IL-l7B mRNA is primarily expressed by the neurons. Immunohistochemical analysis of human spinal cord, dorsal root ganglia, cerebral cortex, cerebellum, and hippocampus demonstrated that IL-17B protein is primarily localized to the neuronal cell bodies and axons (34). IL-17BR was found exclusively in human kidney, pancreas, liver, brain, and intestines (35). IL-17B and IL-17C were cloned and are related to IL-17 A with approximately 27% amino acid identity. Fluorescence-activated cell sorter analysis shows that IL-17B and IL-17C bind and stimulate the monocytic cell line, THP-l, to release TNF-u and IL 1-13 (36). IL-17D is preferentially expressed in skeletal muscle, brain, adipose tissue, heart, lung, and pancreas. Treatment of endothelial cells with purified rIL-17D protein stimulated the production ofIL-6, IL-8, and GM-CSF. The increased expression ofIL-8 was found to be NF-K B-dependent. rIL-17D also demonstrated an inhibitory effect on hemopoiesis of myeloid progenitor cells in colony formation assays (37). IL-17E is a ligand for the recently identified protein termed EVI27/IL-17BR, or IL-17 receptor homolog 1 (lL-17Rh 1). Murine EVI27 was identified by its location at a common site of retroviral integration in BXH2 murine myeloid leukemias. IL-17Rh 1 shows highest level expression in kidney and moderate expression in multiple other

The diffuse excessive high-signal intensity (DEHSI) findings in the T2 weighted scans of white matter (WM), besides the corresponding low signal in the T1 weighted images, are usually more evident around the periventricular regions. It is not clear whether the DEHSI should be considered as a diffuse WM injury rather than a sign of delayed maturation of the WM. Eighty nine preterm infants at the full-term equivalent age (FEA) were studied using conventional Magnetic Resonance (MR) imaging of the brain. Based on the MR findings, the infants studied were divided into three groups: the control group presenting normal WM, the DEHSI group and the group with other WM lesions. Ten newborns were not included in the statistical analysis because they presented evidence of precedent germinal matrix hemorrhage (GMH-IVH) which cannot be considered as WM lesions. Seventy nine infants were enrolled in a program of neuropsychobehavioural study follow-up until 24 months of age. Each infant was evaluated for those variables which mostly affect the occurrence of neuropsychomotor disability. In the DEHSI infant group, significantly lower mean pH and mean base excess (BE) values were found in comparison to controls, while the mean birth weight (BW) was significantly higher. No significant difference was observed between the mean 1st minute Apgar Score, mean birth gestational age (GA) and assisted ventilation mean duration of controls and DEHSI groups. Finally, no significant difference between the parameters studied was found by comparing the WM lesion infants group to the DEHSI infants one. Our observations, together with follow-up studies, even up to school age, confirm that DEHSI has a clinical significance and cannot be considered as a simple indicator of delayed WM maturation.