Inhibition of IL-1β and TNFα Gene Expression by IVIg or Anti-Red Blood Cell Antibodies in a Mouse Model of ITP.
Bibliographic record
Abstract
Abstract Plasma-derived human IgG (IVIg) have been used for more than 2 decades for the treatment of several autoimmune diseases such as ITP, even if their mechanism of action is still not fully understood. Recently, several studies with IVIg-treated patients have shown that IVIg can modulate the serum level of both pro-inflammatory and anti-inflammatory cytokines. In ITP, it is known that the destruction of autoantibody-coated platelets occurs mainly in the spleen. We thus used a mouse model of ITP to evaluate the modulatory effects of IVIg on the expression of several cytokine genes in the spleen of the animals by quantitative RT-PCR. The results showed that the induction of platelet destruction following injection of monoclonal anti-platelet antibodies (MWReg30) in BALB/c mice did not change the expression level of IL-1ra and IL-10 (anti-inflammatory cytokines) and IL-6, IFNγ and MCP-1 (pro-inflammatory cytokines). In contrast, MWReg30-treated mice showed an increase in IL-1β and TNFα mRNA expression by up to 4.2 and 2.1 fold respectively compared to control mice. Treatment of thrombocytopenic mice with IVIg (2g/Kg) prevented the increase of IL-1β mRNA but not TNFα mRNA. In parallel, the effect of anti-red blood cell (anti-RBC) antibodies, used to mimic anti-D treatment of ITP patients, was analysed. The results were similar to those observed with IVIg for IL-1β mRNA, but in contrast to IVIg, anti-RBC treatment also prevented the increase in TNFα gene expression, suggesting that the mechanisms of action of IVIg and anti-D in ITP treatment are different, in agreement with previous studies. In summary, we showed that IVIg and anti-RBC treatments attenuate the expression of important pro-inflammatory cytokines. IL-1β and TNFα are known to increase the phagocytic activity of macrophages and also to enhance the production of antibodies by B cells. Therefore, IVIg and anti-D could contribute to the prevention of platelet destruction in ITP by limiting the activation of phagocytes and the production of autoantibodies. This study was assisted by a grant from the Bayer/CBS/HQ partnership Fund to RB and RL.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".