Controvèrsia en l'aplicació de la llei del medicament. Fàrmacs d'humana vs fàrmacs veterinaris

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Potential use of local and systemic humoral immune response parameters to forecast Mycoplasma hyopneumoniae associated lung lesions

Immunopathological events are key for the development of enzootic pneumonia (EP), which is macroscopically observed as cranioventral pulmonary consolidation (CVPC). This study aimed to investigate the putative association between the humoral immune response against Mycoplasma hyopneumoniae (M. hyopneumoniae) and prevalence and extension of CVPC in 1) experimentally infected pigs, 2) slaughtered pigs and 3) sequentially necropsied pigs in a longitudinal study. CVPC was scored by means of the European Pharmacopoeia recommended methodology. Specific IgG, IgG1 and IgG2 antibodies were assessed in serum. In addition, mucosal IgG and IgA antibodies were analyzed in broncho-alveolar lavage fluid (BALF) from experimentally challenged pigs. The systemic humoral immune response in experimentally infected pigs was delayed in onset whereas humoral respiratory mucosal immune response appeared more rapidly but declined earlier. Although low, BALF IgG antibodies showed the highest correlation with CVPC scores (r = 0.49, p<0.05). In slaughter-aged pigs, both percentage of lungs with CVPC and mean lung lesion score were significantly higher inM. hyopneumoniae seropositive farms compared to the seronegative ones (p<0.001). Similarly, seropositive sequentially necropsied pigs showed more severe CVPC than seronegative ones. Overall, mean serological values might help to forecast prevalence and severity of EP-like lung lesions using a population based approach. Remarkably, the specific systemic humoral immune response was found to be predominated by the IgG2 subclass, suggesting a dominant Th1- mediated immune response toM. hyopneumoniae.This work was supported by a collaborative agreement for independent research from Boehringer Ingelheim and a grant from Secretaria del Departament d'Economia i Creixement de la Generalitat de Catalunya (Industrial Doctorate: DI2013-0039). Boehringer Ingelheim provided support in the form of salaries for authors BGM and TC. The specific roles of BGM and TC are articulated in the ªauthor contributionsº section

Mean S/P ratios and mean IgG1 and IgG2 OD values in sera from pigs sequentially necropsied in the chronological herd study.

<p>*Significant differences among mean IgG1 and IgG2 OD values (<i>p</i><0.05).</p

<i>M</i>. <i>hyopneumoniae</i> serological results from all pigs at all time points and pathological results obtained along sequential necropsies from the chronological herd study.

<p>Different superscripts within a row indicate significant differences between weeks of age (<i>p</i><0.05). NA, non-available.</p

Potential use of local and systemic humoral immune response parameters to forecast <i>Mycoplasma hyopneumoniae</i> associated lung lesions - Fig 3

<p><b>Mean <i>M</i>. <i>hyopneumoniae</i> IgG (A) and IgA (B) OD values (±SD) in BALF samples from animals of the experimental study with and without CVPC at 21 and 28 dpi.</b> Different superscripts indicate significant differences of antibody levels among animals with and without CVPC at 21 and 28 dpi (<i>p</i><0.05). Discontinuous line represents the positivity threshold.</p

Potential use of local and systemic humoral immune response parameters to forecast <i>Mycoplasma hyopneumoniae</i> associated lung lesions

<div><p>Immunopathological events are key for the development of enzootic pneumonia (EP), which is macroscopically observed as cranioventral pulmonary consolidation (CVPC). This study aimed to investigate the putative association between the humoral immune response against <i>Mycoplasma hyopneumoniae</i> (<i>M</i>. <i>hyopneumoniae</i>) and prevalence and extension of CVPC in 1) experimentally infected pigs, 2) slaughtered pigs and 3) sequentially necropsied pigs in a longitudinal study. CVPC was scored by means of the European Pharmacopoeia recommended methodology. Specific IgG, IgG1 and IgG2 antibodies were assessed in serum. In addition, mucosal IgG and IgA antibodies were analyzed in broncho-alveolar lavage fluid (BALF) from experimentally challenged pigs. The systemic humoral immune response in experimentally infected pigs was delayed in onset whereas humoral respiratory mucosal immune response appeared more rapidly but declined earlier. Although low, BALF IgG antibodies showed the highest correlation with CVPC scores (r = 0.49, <i>p</i><0.05). In slaughter-aged pigs, both percentage of lungs with CVPC and mean lung lesion score were significantly higher in <i>M</i>. <i>hyopneumoniae</i> seropositive farms compared to the seronegative ones (<i>p</i><0.001). Similarly, seropositive sequentially necropsied pigs showed more severe CVPC than seronegative ones. Overall, mean serological values might help to forecast prevalence and severity of EP-like lung lesions using a population based approach. Remarkably, the specific systemic humoral immune response was found to be predominated by the IgG2 subclass, suggesting a dominant Th1-mediated immune response to <i>M</i>. <i>hyopneumoniae</i>.</p></div

Mean Ph. Eur. Score (±SD) and percentage of affected lungs by CVPC (±SD) in seropositive and seronegative farms from the slaughterhouse study.

<p>Different superscripts within a row indicate significant differences among types of farms (<i>p</i><0.05).</p

Immunopathological data obtained from the experimental study.

<p><b>Number (%) of animals showing CVPC, mean Ph. Eur. Score (± SD), mean S/P ratio (± SD) and number (%) of seropositive (IgG) and positive animals to <i>M</i>. <i>hyopneumoniae</i>-IgG1 and IgG2 in sera and to IgG and IgA antibodies in BALF at 21 and 28 dpi.</b> Different superscripts within a column indicate significant differences among days post-inoculation (<i>p</i><0.05).</p

Parameters and samples evaluated within the experimental, slaughterhouse and chronological herd studies.

<p>Macroscopic lung lesions were quantified by the European Pharmacopoeia (Ph. Eur., monograph number 04/2013:2448) lung scoring system. All humoral immune parameters were assessed by ELISA technique.</p