Cytokine profiles in mouse models of experimental immune thrombocytopenia reveal a lack of inflammation and differences in response to intravenous immunoglobulin depending on the mouse strain
Bibliographic record
Abstract
BACKGROUND: Mouse models of human immune thrombocytopenia (ITP) have been used for years to investigate the mechanism of intravenous immunoglobulin (IVIG) to ameliorate ITP; however, how closely these experimental mouse models mirror the human autoimmune inflammatory disease is unclear. The aim of this study was to assess the cytokine profiles in experimental ITP with and without IVIG treatment. STUDY DESIGN AND METHODS: We examined the production of 23 cytokines that included pro- and anti-inflammatory cytokines, in two different mouse strain models of ITP, BALB/c and C57BL/6J, with and without IVIG treatment. RESULTS: In contrast to human ITP, in mouse models of ITP generated by passive transfer of an alloantibody we find no evidence of inflammatory disease even when ITP is robust, suggesting that while these models capture the innate response phase of the disease, they may not be capturing the adaptive mechanisms of autoimmune initiation of the disorder. Regardless of the mouse strain examined, interleukin (IL)-1α, -2, -6, -17, and -23; granulocyte-macrophage-colony-stimulating factor (GM-CSF); monocyte chemoattractant protein (MCP)-1; macrophage inflammatory protein (MIP)-1β; RANTES; tumor necrosis factor (TNF)-α; and interferon-γ remain at negligible levels after ITP induction. IVIG treatment in the absence of ITP induced significant levels of IL-4, -10, -11, -17, and -23; GM-CSF; MCP-1; and TNF-α in BALB/c mice, but only IL-11 was elevated in C57BL/6J mice. In response to IVIG treatment of ITP, both strains produced IL-4, -10, -11, and -23; GM-CSF; MCP-1; MIP-1β; and TNF-α; however, only BALB/c exhibited increased MCP-3 and RANTES. IL-11 levels were the highest of any cytokine after IVIG administration, given either alone or as treatment of ITP. CONCLUSIONS: We conclude that mouse models for human ITP do not capture the full range of autoimmune inflammatory mechanisms of this disease. Furthermore, cytokine profiles differ in response to IVIG depending on the mouse strain used.
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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 | 0.000 | 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 | 0.000 |
| 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".