Evolutionarily conserved mechanisms regulating stress-induced neutrophil redistribution in fish.

Introduction: Stress may pose a serious challenge to immune homeostasis. Stress however also may prepare the immune system for challenges such as wounding or infection, which are likely to happen during a fight or flight stress response. Methods: In common carp (Cyprinus carpio L.) we studied the stress-induced redistribution of neutrophils into circulation, and the expression of genes encoding CXC chemokines known to be involved in the regulation of neutrophil retention (CXCL12) and redistribution (CXCL8), and their receptors (CXCR4 and CXCR1-2, respectively) in blood leukocytes and in the fish hematopoietic organ - the head kidney. The potential involvement of CXC receptors and stress hormone receptors in stress-induced neutrophil redistribution was determined by an in vivo study with selective CXCR inhibitors and antagonists of the receptors involved in stress regulation: glucocorticoid/mineralocorticoid receptors (GRs/MRs), adrenergic receptors (ADRs) and the melanocortin 2 receptor (MC2R). Results: The stress-induced increase of blood neutrophils was accompanied by a neutrophil decrease in the hematopoietic organs. This increase was cortisol-induced and GR-dependent. Moreover, stress upregulated the expression of genes encoding CXCL12 and CXCL8 chemokines, their receptors, and the receptor for granulocytes colony-stimulation factor (GCSFR) and matrix metalloproteinase 9 (MMP9). Blocking of the CXCR4 and CXCR1 and 2 receptors with selective inhibitors inhibited the stress-induced neutrophil redistribution and affected the expression of genes encoding CXC chemokines and CXCRs as well as GCSFR and MMP9. Discussion: Our data demonstrate that acute stress leads to the mobilization of the immune system, characterized by neutrophilia. CXC chemokines and CXC receptors are involved in this stress-induced redistribution of neutrophils from the hematopoietic tissue into the peripheral blood. This phenomenon is directly regulated by interactions between cortisol and the GR/MR. Considering the pivotal importance of neutrophilic granulocytes in the first line of defense, this knowledge is important for aquaculture, but will also contribute to the mechanisms involved in the stress-induced perturbation in neutrophil redistribution as often observed in clinical practice.

New onset Graves' disease as a cause of an adrenal crisis in an individual with panhypopituitarism: brief report.

UNLABELLED: : 46 year old patient was admitted as an emergency with vomiting, hypotension and serum cortisol of 0,940 mug/dl (26 nmol/l) indicative of adrenal failure. Despite previous history of panhypopituitarism he was found to be hyperthyroid [free T4 6.32 ng/dl (ref. range: 0.93-1.7), free T3 22.21 pg/ml (ref. range: 1.8-4.6)]. He was fit and well till the age of 45. Eight months prior to this hospitalisation he presented with diabetes insipidus and was found to have a large cystic tumour in the area of the pituitary gland. Surgery was only partially successful and histologically the tumour was diagnosed as craniopharyngioma. Endocrine assessment revealed deficiency in ACTH-cortisol, growth hormone, and gonadotropin, as well as low-normal free T4. On the day of his emergency admission he looked ill and dehydrated, though was fully conscious and cooperative. Heart rate was 120 beats/min (sinus rhythm), blood pressure 85/40 mm Hg. There were no obvious features of infection, but there was marked tremor and thyroid bruit. He received treatment with intravenous fluids and hydrocortisone. L-thyroxine was stopped. Administration of large dose of methimazole (60 mg/day) resulted in gradual decrease in free T4 and free T3 (to 1.76 ng/ml, and 5.92 pg/ml, respectively) over a 15-day period. The patient was found to have increased titre of antithyroperoxidase (anti-TPO) and anti-TSH receptor (anti-TSHR) antibodies [2300 IU/l (ref. range <40) and 3.6 IU/l (ref. range <1.0), respectively]. He was referred for radioactive iodine treatment. Iodine uptake scan performed prior to radioiodine administration confirmed uniformly increased iodine uptake consistent with Graves' disease. CONCLUSION: Our case illustrates coexistence of hypopituitarism and clinically significant autoimmune thyroid disease. The presence of hypopituitarism does not preclude the development of autoimmune thyrotoxicosis.

Expression of insulin-like growth factor I (IGF-I) gene and of genes for IGF-binding proteins 1, 2, 3, 4 (IGFBP-1-IGFBP-4) in non-neoplastic human thyroid cells and in certain human thyroid cancers. Effect of exogenous IGF-I on this expression.

AIM: The aim of this study was to examine the expression of the IGF-I gene and of genes for IGFBP-1, -2, -3, and -4 in cells from nodular goiters (NG), and from different human thyroid carcinomas (papillary--PTC, anaplastic--ATC, and medullary--MTC), cultured in monolayers. The influence, exerted by exogenous IGF-I on the expression of these genes, was also investigated. METHODS: Thyroid tissue specimens were obtained from 65 patients during subtotal or total thyroidectomies. After approximately 2-3 weeks of culture, thyroid cells were incubated for 24 hours with IGF-I in concentrations of: 0, 1, 10 and 100 ng/ml. The total mRNA was isolated according to the method described by Chomczynski and Sacchi with our own modifications. Afterwards, mRNA encoding IGF-I, IGFBP-1-IGFBP-4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were amplified, using the reverse transcription-polymerase chain reaction (RT-PCR); GAPDH gene served as a control gene. PCR products were electrophoresed and then submitted to densitometric analysis. RESULTS AND CONCLUSIONS: Our study has shown that in carcinoma cells (ATC, PTC, MTC), IGF-I reveals a stimulatory influence on the expression of its own gene, that effect being most distinctive in ATC cells. These facts indicate an important role of IGF-I in the pathogenesis and invasiveness of the analyzed malignant neoplasms.