Effects of Arginine Vasopressin (AVP) Deficiency, Conivaptan and Desmopressin on Clinical Symptoms and Blood Cytokine Levels in Rats with Experimental Autoimmune Encephalomyelitis
Bibliographic record
Abstract
Introduction The experimental autoimmune encephalomyelitis (EAE), the rat paradigm for the human multiple sclerosis (MS), are autoimmune diseases mediated by Th1 and Th17 cells and responsible of the nervous system demyelination and progressive paralysis. It is know that lymphocytes possess AVP receptors and that EAE increases AVP serum levels along the disease. Neurointermediate pituitary lobectomy (NIL) in rats causes AVP and oxytocin permanent low serum levels and decreased humoral and cell‐mediated immune responses. Nevertheless the role of AVP as a direct immune regulatory factor has not been well clarified. Objective To investigate the effects of AVP deficiency (by NIL), and the treatment with desmopressin (DP, a synthetic analog of AVP) and conivaptan (CNV, an AVP V1a‐V2 receptor antagonist) on the clinical symptoms of EAE, and to determine the serum levels of Interleukine‐2 (IL‐2), IL‐4, IL‐6, IL‐10, IL‐17A, INF‐γ and TNF‐α in the experimental groups. Methods Groups of female Lewis rats were divided in: (1) Intact control (Control) (2) Control+EAE, (3) Sham‐operated (SHAM), (4) Control+CNV, (5) NIL and (6) NIL+DP. Except the Control the remaining groups were immunized for EAE three weeks post‐NIL. DP and CNV administrations started 3 days before EAE immunizations. Serum cytokines were analyzed by flow cytometry and EAE clinical symptoms were evaluated by a conventional numerical scale. Results EAE clinical symptoms, INF‐γ, TNF‐α, and the IL‐2, IL‐6 and IL‐17A were significantly decreased in both NIL and CNV groups, whereas the IL‐4 and IL‐10 increased in the CNV group. In NIL+DP group we found a significant increase in TNF‐α, whereas the IL‐4 was significantly decreased. Conclusions 1) The present clinical and molecular findings demonstrate that AVP deficiency and the block of the AVP receptors decreased immune response, and that DP restores the susceptibility of the NIL animals to develop EAE. 2) The results strongly support that acting directly on the AVP receptors, AVP plays an important immuneregulatory role in the generation and maintenance of the immune‐competence, 3) AVP receptors may be therapeutic targets in the treatment of the human MS. Support or Funding Information Supported by UAA‐PIFF14‐1 and CONACYT‐221262 (AQS). México . This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".