The presence of ongoing chronic inflammation in chronic RHD is well known. Some studies have shown that it is related to the development of valvular lesions [4]. In fact, some authors [4, 5] found that the serum levels of inflammatory markers were correlated to the severity of the valvular lesions. Davutoglu et al. showed that chronic RHD was associated with high serum inflammatory mediators which correlated strongly with the severity of valve lesion, valve scarring, subsequent valve calcification, and decreased functional status. They recommended that further research was needed to indicate whether anti-inflammatory drugs might reduce progression of the valvular lesions as well as morbidity and mortality in patients with chronic RHD [4].
In our study, we investigated the effect of colchicine as anti-inflammatory drug on the serum levels of inflammatory markers CRP and IL-6 In chronic RHD. To our knowledge, this is the first study to address the effect of colchicine as anti-inflammatory drug on the serum levels of inflammatory markers CRP and IL-6 in chronic RHD. The baseline of the serum inflammatory markers CRP and IL-6 before starting the colchicine treatment showed significant difference between the patients and the control group. This confirms the presence of the ongoing inflammation in chronic RHD patients, in accordance with other studies [4,5,6].
Soares and his colleagues investigated the cytokine plasma levels in patients with chronic RHD as possible markers for the severity of the disease; the study concluded that high levels of inflammatory cytokines were correlated with the severity of RHD. Moreover, the co-regulated expression of IL-6 and TNF-α was associated with a worse clinical presentation [7]. On looking at our results, patients showed highly significant reduction in the serum inflammatory markers after 1 month of receiving colchicine 0.5 mg twice daily on regular basis. CRP was 6.09 ± 4.39 (IU/ml) before and 3.34 ± 3.07 (IU/ml) after colchicine. IL-6 was 113.57 ± 37.41 (ng/L) before and 45.57 ± 20.39 (ng/L) after colchicine (P = 0.0001).
Whether this significant drop of IL-6and CRP might slow down the rheumatic process and thus ameliorate the valvular lesions is still to be proven. However, it is possible that a better inflammatory status might be translated to clinical benefit especially on long-term follow-up since chronic inflammation appears to have a major role in the progression of valvular damage in patients with RHD [4, 5].
We have previously shown [8] that patients with mitral restenosis after balloon mitral valvuloplasty had higher serum levels of IL-6 and CRP than those who do not have restenosis. This adds to the evidence that progression of valve lesions may be related to higher inflammatory burden. One could wonder about the exact cause of this inflammatory state seen in RHD patients and whether or not genetic factors might play a role at least in the susceptibility and immune response to RF.
Beltrame et al. and more recently Gomaa et al. found that high mannose-binding lectin (MBL) levels increased the risk of RHD and that genotypes associated with high MBL production were associated with both acute and chronic rheumatic carditis. One suggested mechanism was that MBL elicited inflammation and complement tissue damage even in the chronic stage of the disease [9, 10].
Rehman et al. in 2013 studied the role of cytokine gene polymorphisms and their potential usefulness as biomarkers in RHD patients. The study concluded that TNF-α (-308) and IL-6(-174) polymorphisms may be useful markers for the identification of individuals susceptible to RHD. It is plausible that genetics may play a role in perpetuating the chronic inflammatory state seen in patients with RHD. However, further studies are needed to elucidate its precise role [11].
We found that in the three regimens used for RF penicillin prophylaxis, the basic serum level of inflammatory markers was significantly higher in the 30-day regimen than in 15 and 21 days. Moreover, the effect of colchicine on IL-6 and CRP was more marked in the 21- and 15-day than in the 30-day regimen. This might be due to type 1 statistical error due to the small number receiving 30-day regimen. We have recently shown [12] that there is a strong negative correlation between serum levels of inflammatory markers (IL-6 and CRP) and serum penicillin in RHD. The exact mechanism of this finding is unclear. We think it might be related to some anti-inflammatory or anti-streptococcal action of penicillin. Thus, it seems that it is better to use either the 21- or15-day rather than the 30-day regimen of penicillin prophylaxis.