In the present study, we examined the PF and blood eosinophilia in patients with post-CABG EPEs and non-EPEs, and their possible association with PF and blood levels of IL-5, eotaxin-2, eotaxin-3, and VCAM-1. Our main findings were as follows: (1) the percentage and the number of PF eosinophils correlated significantly with the percentage and the number of blood eosinophils, respectively; (2) PF IL-5 levels were significantly higher than the corresponding serum IL-5 levels in every patient with a post-CABG pleural effusion (there was a significant correlation between the PF and serum IL-5 levels), and PF and serum IL-5 levels correlated significantly with the number and the percentage of PF and blood eosinophils, respectively; (3) PF eotaxin-3 levels were significantly higher than the corresponding serum levels, but there was no significant correlation between PF and serum eotaxin-3 levels, with PF eotaxin-3 levels correlating significantly with the number and the percentage of PF eosinophils; (4) PF eotaxin-2 levels were significantly lower than the corresponding serum levels, and there was a significant correlation between the PF levels and the corresponding serum levels, with PF or serum eotaxin-2 levels not differing significantly between patients with EPEs and those with non-EPEs (no correlation between PF eotaxin-2 levels and PF eosinophil levels); and (5) PF VCAM-1 levels were significantly lower than the corresponding serum levels, and there was no significant correlation between PF and serum levels, with PF VCAM-1 levels being significantly higher in EPEs than in non-EPEs, but there was no correlation between PF VCAM-1 levels and PF eosinophil levels.
Peripheral blood eosinophilia is a common finding in patients with EPEs of different etiologies, but it is not always present in patients with mechanical pleural injury. Our findings suggest a strong association between PF and peripheral blood eosino-philia in patients with post-CABG EPEs. In agreement with previous observations in posttraumatic EPEs,” the eosinophil percentage in the PF was always higher than that in the blood. This observation probably reflects the fact that eosinophils, produced in the bone marrow, have a very short half-life in the blood, being rapidly attracted into the pleural space. The absence of peripheral blood eosinophils in a minority of patients with post-CABG EPEs may indicate that the eosinophilic reaction had started to regress in these patients. The clinical implication of the above findings is that the presence of blood eosinophilia in a patient with a post-CABG pleural effusion is suggestive of PF eosinophilia. However, blood eosinophilia should not be considered as an absolute indicator for PF eosinophilia, since it was not observed in every patient with an EPE, and it was also found in a minority of patients (4 of 25 patients) with a non-EPE. Do you want to know what it meand to suffer from chronic disease? The answer is here – All news that you need at Canadian health care website.
In the present study, we examined for the first time both PF and serum concentrations of different proteins that are known to contribute to eosinophilic inflammation in patients with EPEs and non-EPEs.
Our results indicate a strong association between IL-5 and the eosinophilic reaction in response to pleural injury induced by CABG surgery. We showed that PF IL-5 levels were significantly higher in patients with post-CABG EPEs than in those with post-CABG non-EPEs, and that PF IL-5 levels correlated significantly with the number and the percentage of PF eosinophils. This finding confirms previous observations’ concerning the role of IL-5 in the pathogenesis of EPEs of different etiologies.
The present study demonstrates that the median PF IL-5 level was significantly higher than the corresponding serum level, and that there was a significant correlation between the PF and serum IL-5 levels. This observation suggests that IL-5 is produced in the pleural cavity and that a portion of the cytokine enters the bloodstream. The notion of the local production of IL-5 in the pleural space was initially raised by Schandene and coworkers, who reported that IL-5 was produced by PF but not blood CD4+ lymphocytes in three patients with posttraumatic EPEs. Our study not only confirms in a larger number of patients that IL-5 is produced locally in the pleural compartment in EPEs associated with mechanical pleural injury, but also shows for the first time that PF levels of this cytokine are higher than the corresponding serum levels, even in patients with post-CABG non-EPEs. Accordingly, one can speculate that pleural IL-5 production is commonly induced by CABG surgery but that it does not always lead to the accumulation of eosinophils in the pleural cavity, suggesting that other cytokines and adhesion molecules are necessary for the development of postsurgical EPEs.
We also observed that serum IL-5 levels were significantly higher in patients with EPEs than in those with non-EPEs, and that they correlated significantly with the number and the percentage of blood eosinophils, a finding that implies a role for serum IL-5 in the pathogenesis of pleural eosino-philia. Thus, combining the observations made of PF and serum, we could speculate that mechanical irritation of the pleura caused by surgery induces the production of IL-5 in the pleural cavity, followed by a spill of the cytokine into the circulation and subsequent stimulation of eosinophilopoiesis in the bone marrow. As a result, the number of circulating eosinophils increased. Eosinophil chemoattractants and adhesion molecules are then required to complete the translocation of the eosinophils from the blood to the pleural cavity.
Chemokines are cytokines with chemotactic activity for inflammatory cells. Among them, the eotaxins (—1, —2, and —3) are potent eosinophil chemoat-tractants and activators, and they participate in the pathogenesis of eosinophilic human diseases.’ Moreover, some data have suggested that they may also prolong eosinophil survival. Yokoyama and coworkers reported that PF eotaxin-1 (CCL-11) levels were higher in EPEs than in non-EPEs and that they correlated with the number of PF eosinophils. However, this finding was not confirmed by a previous study performed by our group.
In the present study, we examined the levels of eotaxin-2 (CCL-24) and eotaxin-3 (CCL-26), which share the same receptor with eotaxin-1 and have the same effects on eosinophils as eotaxin-1. This is the first report on eotaxin-2 and eotaxin-3 levels in pleural effusions. PF eotaxin-3 levels were significantly higher than the matched serum levels, suggesting that eotaxin-3 is produced locally in the pleural space in patients with post-CABG pleural effusions. PF eotaxin-3 levels were significantly higher in EPEs than in non-EPEs and correlated with the number of the PF eosinophils, findings that suggest that eotaxin-3 is involved in EPE pathogenesis. The low concentration of eotaxin-3 in serum and the absence of any significant difference in serum levels between patients with EPEs and those with non-EPEs suggests that increased serum levels of eotaxin-3 are not important for eosinophil recruitment in the pleural space and that the chemotactic activity of this chemokine is restricted to eosinophils passing through the pleural vasculature. In agreement with our assumption that eotaxin-3 participates in the pleural localization of eosinophils, Cuvelier and Patel showed that the transmigration of eosinophils on activated endothelial cells is regulated by eotaxin-3.
PF levels of eotaxin-2 were significantly lower than its corresponding serum levels, and there was a significant correlation between the PF levels of the chemokine and the corresponding serum levels. These findings suggest that eotaxin-2 is not preferentially produced in the pleural cavity and that its presence in the PF may be the result of diffusion from the blood. Moreover, our findings imply that eotaxin-2 does not have a role in the pathogenesis of post-CABG EPEs, since its PF levels did not differ between patients with EPEs and those with non-EPEs, and did not correlate with the PF eosinophil counts or percentages. In agreement with our findings, other investigators have reported that eotaxin-3 is more important than eotaxin-2 in the tissue eosinophil accumulation that occurs in patients with allergic diseases.”
VCAM-1 is an adhesion molecule that is expressed on the surface of endothelial cells and mediates the recruitment of eosinophils at sites of inflammation. We have previously reported that PF VCAM-1 levels are higher in EPEs than in non-EPEs, and that they correlate with the number and the percentage of PF eosinophils. One of the questions raised from this previous study was whether VCAM-1 is locally produced in the pleural cavity. The results of the present study do not support this possibility since the serum VCAM-1 levels were significantly higher than the PF VCAM-1 levels. Although we confirmed that the PF VCAM-1 levels were higher in EPEs than in non-EPEs, we did not find a significant correlation between PF VCAM-1 levels and either the number or the percentage of PF eosinophils in the present study. Hence, although it is likely that VCAM-1 mediates the transmigration of eosinophils into the pleural cavity, its importance in the production of EPEs remains to be elucidated.
It is interesting to note that a minority of post-CABG pleural effusions included in the present study were eosinophilic. This could be explained by the timing of the development of the pleural effusions included in the study since previous observa-tions have suggested that pleural effusions occurring later than the first month after surgery usually do not contain increased numbers of eosinophils. However, this explanation is not likely since, in the present study, EPEs were not found to occur earlier than non-EPEs and the median latent time of both was < 30 days. PF eosinophilia could be also attributed to the bloody nature of some effusions. Again, this assumption was not supported by the results of the present study since PF eosinophil levels did not correlate with the PF RBC count. Thus, It is unclear why some post-CABG pleural effusions are eosinophilic while others are not. This phenomenon can be due to differences in the severity of pleural injury during the operation or may represent different individual responses that are influenced by genetic factors. Whatever the underlying mechanism, the present study strongly suggests that IL-5 and eotaxin-3 are involved in the pathogenesis of post-CABG-associated PF eosinophilia.
In conclusion, our results indicate that in patients with post-CABG pleural effusions, IL-5 and eotaxin-3 are produced in the pleural cavity, and participate in the pathogenesis of PF eosinophilia. Furthermore, it is likely that increased serum IL-5 levels result from an overflow from the pleural compartment, and may potentially stimulate increased production and mobilization of eosinophils from the bone marrow and their accumulation in the PF. VCAM-1 levels are elevated in EPEs and may participate in EPE pathogenesis. We also showed that in a patient with post-CABG pleural effusions, the presence of peripheral blood eosinophilia suggests that the effusions are eosinophilic.