Cytokine and acute phase protein gene expression in repeated liver biopsies of dairy cows with a lipopolysaccharide-induced mastitis
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Bibliographic record
Abstract
A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6, and IL-10, and the acute phase proteins serum amyloid A isoform 3 (SAA3), haptoglobin (Hp), and alpha(1)-acid glycoprotein (AGP) were determined by real-time reverse transcription-PCR. Fourteen primiparous cows in mid lactation were challenged with 200 microg of LPS (n = 8) or NaCl solution (n = 6) in 1 front quarter. Six repeated liver biopsies were collected at -22, 3, 6, 9, 12, and 48 h relative to LPS challenge in 4 LPS-infused cows and 3 NaCl-infused cows. The remaining cows had 3 liver biopsies taken at -22, 9, and 48 h. Production data and clinical signs were recorded and white blood cell counts and somatic cell counts (SCC) were analyzed to investigate the effect of repeated liver biopsies and verify the LPS model. Plasma concentrations of TNF-alpha, SAA3, Hp, and AGP were determined for comparison with the liver expression data. Repeated liver biopsies had no effects on the production data, clinical signs, or APR of dairy cows. Compared with the NaCl-infused cows the LPS-infused cows responded to the LPS treatment by increased body temperature (38.6 +/- 0.1 vs. 39.4 +/- 0.1 degrees C), short-term leukopenia followed by leukocytosis (6.44 +/- 0.4 vs. 5.69 +/- 0.3 x 10(6) cells/mL), an increased SCC (log(10) 2.1 +/- 0.1 vs. log(10) 2.8 +/- 0.1 x 10(3) cells/mL), heart rate (76 +/- 1 vs. 93 +/- 1 beats/min), and respiratory rate (32 +/- 2 vs. 36 +/- 1 breaths/min) in the acute phase of the disease. The LPS treatment upregulated the hepatic expression of TNF-alpha (103 +/- 24 vs. 255 +/- 18 units), IL-1beta (37 +/- 23 vs. 296 +/- 18 units), IL-6 (8 +/- 17 vs. 122 +/- 12 units), and IL-10 (130 +/- 66 vs. 541 +/- 50 units), and SAA3 (64 +/- 36 vs. 128 +/- 28 units) and Hp (9 +/- 82 vs. 762 +/- 65 units) reaching maximum levels at 3 to 6 h and 9 to 12 h postinfusion, respectively. Plasma concentrations of TNF-alpha (nondetectable vs. 1.9 +/- 0.3 ng/mL), SAA (19.8 +/- 19.4 vs. 149.7 +/- 15.5 microg/mL) and Hp (71.4 +/- 143.7 vs. 1,013.8 +/- 111.5 microg/mL) were elevated in the LPS-infused cows at 4 to 12 h, 8 to 120 h, and 24 to 120 h postinfusion, respectively. The hepatic expression of AGP and the AGP plasma concentration remained unaltered in LPS-induced cows. In conclusion, a minimally invasive liver biopsy technique can be used for studying the hepatic APR in diseased cattle. Lipopolysaccharide-induced mastitis resulted in a time-dependent production of inflammatory cytokines and SAA and Hp in the liver of dairy cows.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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 it