Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis

Abstract

Feline infectious peritonitis virus (FIPV) replication in macrophages/monocytes induced tumor necrosis factor (TNF)-alpha production, and that the TNF-alpha produced was involved in aggravating the pathology of FIP. We previously reported the preparation of a feline TNF-alpha (fTNF-alpha)-neutralizing mouse monoclonal antibody (anti-fTNF-alpha mAb). This anti-fTNF-alpha mAb 2-4 was confirmed to inhibit the following fTNF-alpha-induced conditions in vitro. In the present study, we investigated whether mAb 2-4 improved the FIP symptoms and survival rate of experimentally FIPV-inoculated SPF cats. Progression to FIP was prevented in 2 out of 3 cats treated with mAb 2-4, whereas all 3 cats developed FIP in the placebo control group. Plasma alpha1-glycoprotein and vascular endothelial growth factor levels were improved by the administration of mAb 2-4, and the peripheral lymphocyte count also recovered. These results strongly suggested that the anti-fTNF-alpha antibody is effective for the treatment of FIP.

Keywords: Feline coronavirus; Feline infectious peritonitis; Tumor necrosis factor-alpha.

Fig. 1

The experimental schedule of the anti fTNF-alpha mAb (mAb 2–4) treatment for FIPV-infected cats.

Fig. 2

The changes on plasma alpha1-acid glycoprotein (AGP) concentration of FIPV-infected cats treated with mAb 2–4. The normal value of AGP is 386 ± 60 μg/ml (quoted from the manufacturer's protocol, mean ± S.D.). Gray bar; group A, black bar; group B. N.S.: not significant.

Fig. 3

The changes on plasma vascular endothelial growth factor (VEGF) concentration of FIPV-infected cats treated with mAb 2–4. Gray bar; group A, black bar; group B. N.S.: not significant.

Fig. 4

The changes on neutrophil counts and percentages of neutrophils of FIPV-infected cats treated with mAb 2–4. (A) Neutrophil counts in peripheral blood. (B) Percentage of neutrophils on differential blood cell counting. †: Animal was euthanized because its critical condition reached the humane endpoint.

Fig. 5

The changes on lymphocyte counts and lymphocyte subsets of FIPV-infected cats treated with mAb 2–4. (A) Lymphocyte counts in peripheral blood. (B) CD4 + T lymphocyte counts in peripheral blood. (C) CD8 + T lymphocyte counts in peripheral blood. †: Animal was euthanized because its critical condition reached the humane endpoint.

Fig. 6

The changes in body temperature and body weight of FIPV-infected cats treated with mAb 2–4. (A) Body temperature. (B) Body weight. †:Animal was euthanized because its critical condition reached the humane endpoint.

Fig. 7

Survival rate of FIPV-infected cats treated with mAb 2–4. Animals which reached the humane endpoint with no prospect of survival were euthanized.