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Immunomodulating dose of levamisole stimulates innate immune response and prevents intestinal damage in porcine rotavirus diarrhea: a restricted-randomized, single-blinded, and placebo-controlled clinical trial

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Abstract

A restricted-randomized, single-blinded, placebo-controlled clinical trial was conducted to examine whether immunomodulating dose of levamisole (LMS) can stimulate certain antiviral immune markers by measuring the concentrations of interferon-γ (IFN-γ), nitric oxide (NOx), and total immunoglobulin G (IgG); prevents the gut injury; and reduces fecal consistency and dehydration scores in rotavirus type A (RVA)-positive piglet diarrhea. The trial was executed between November 2015 and May 2016 in an institute owned experimental swine production farm. The naturally RVA-exposed diarrheic piglets were used in the study. The piglets born between November 2015 and May 2016, age group of 0 to 2 weeks and confirmed for RVA-positive diarrhea, were randomized to receive supportive treatment (ST) or ST along with levamisole (LMS + ST) at immunomodulating dose. Simultaneously, six piglets were randomly selected from healthy population and kept as placebo control. The primary outcome was reduction of fecal consistency and dehydration scores (≤ 1) over the trial period. The secondary outcome was reduction of concentration of gut injury marker and stimulation of immunomodulatory function. The LMS + ST treatment progressively improved the total leukocyte, neutrophil count, IgG concentration (p < 0.05), and reduced the intestinal fatty acid-binding protein 2 (IFABP-2) concentration in RV-positive diarrheic piglets than ST only. Although NOx and IFN-γ concentrations were enhanced initially on day 3, however, the values reduced significantly on day 5 in response to LMS + ST compared to ST. Interestingly, the scores of fecal consistency and dehydration of RVA-positive diarrheic piglets were dropped much earlier (on day 3) in response to LMS + ST than ST alone. The results indicate that LMS along with supportive treatment non-specifically modulated innate immunity and restored intestinal gut health, and thus, LMS may represent an additional therapeutic agent for management of RVA-inflicted piglet diarrhea.

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Abbreviations

LMS:

Levamisole

IFN-γ:

Interferon-γ

NOx:

Nitric oxide

IgG:

Immunoglobulin G

IFABP-2:

Intestinal fatty acid-binding protein 2

RVA:

Rotavirus type A

ST:

Supportive treatment

NSP1:

Non-structural protein 1

RNA-PAGE:

Ribonucleic acid-polyacrylamide gel electrophoresis

RT-PCR:

Reverse transcription polymerase chain reaction

PBMCs:

Peripheral blood mononuclear cells

cDNA:

Complimentary DNA

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Acknowledgements

The study was supported by All India Network Programme on Neonatal Mortality project of ICAR. CGE and JG thank ICAR-IVRI for granting research fellowship for their research program.

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Author notes

  1. Gollahalli Eregowda Chethan

    Present address: Department of Veterinary Medicine, CVSc & AH, CAU, Selesih, Aizawl, Mizoram, 796014, India

Authors and Affiliations

  1. Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

    Ujjwal Kumar De & Jugal Garkhal

  2. Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

    Shubhankar Sircar & Yash Pal Singh Malik

  3. Livestock Production and Management Section, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

    Nihar Ranjan Sahoo

  4. Division of Bacteriology and Mycology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

    Abhishek

  5. Division of Livestock Economics, Statistics and Information Technology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

    Med Ram Verma

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  1. Gollahalli Eregowda Chethan
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Animal studies were carried out humanely and according to national and international Animal Care and Use Committee protocols and following the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India (approval number F.25/08/2016-CPCSEA).

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Chethan, G.E., Kumar De, U., Garkhal, J. et al. Immunomodulating dose of levamisole stimulates innate immune response and prevents intestinal damage in porcine rotavirus diarrhea: a restricted-randomized, single-blinded, and placebo-controlled clinical trial. Trop Anim Health Prod 51, 1455–1465 (2019). https://doi.org/10.1007/s11250-019-01833-1

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