Balance entre citocinas pro y antiinflamatorias en estados sépticos / The balance between pro-inflammatory and anti-inflammatory citokines in septic states

Para que la defensa contra la infección se inicie de manera eficaz es necesaria la participación de citocinas con función fundamentalmente proinflamatoria (TNF-α, IL-1 ß, IL-12, IFN-γ, IL-6). La respuesta proinflamatoria inicial está controlada por moléculas antiinflamatorias (el antagonista del receptor de la IL-1 [IL-1 ra], el factor transformador del crecimiento beta [TGF-ß], las interleucinas 4, 6, 10, 11 y 13), y los receptores específicos para la IL-1, el TNF y la interleucina 18. En condiciones fisiológicas, todas estas moléculas sirven como inmunomoduladoras y, por lo tanto, limitan el efecto potencialmente dañino de la reacción inflamatoria. Sin embargo, en condiciones patológicas, la respuesta antiinflamatoria puede ser insuficiente para contrarrestar la actividad inflamatoria o, por el contrario, ser sobrecompensadora e inhibir el sistema inmune y dejar al huésped a merced de la infección. Desde el principio del cuadro de sepsis hasta el vigesimo octavo día y cuando ya han desaparecido la clínica de síndrome de respuesta inflamatoria sistémica (SIRS), el balance global entre las moléculas pro y antiinflamatorias estudiadas apunta hacia un incremento muy importante de estas últimas. El papel del TNF-α y de la IL-1 ß en la sepsis parece ser el de desencadenante, pero ambas carecen de valor patogénico posteriormente. El sTNFR-I, sTNFR-II e IL-1 ra, tienen un gran valor pronóstico y sus niveles se relacionan con el desarrollo de síndrome de disfunción multiorgánica (SDMO) y con cada fallo de órganos. Niveles elevados de IL-10 y de TGF-ß también se relacionan con la mortalidad, aunque de modo más tardío. Futuras intervenciones terapéuticas deberán tener en cuenta que la sepsis es un proceso dinámico

The participation of citokines with a predominant pro-inflammatory function (TNF-α, IL-1 ß, IL-12, INF-γ, IL-6) is necessary for the effective beginning of defense mechanisms against infection. Initial pro-inflammatory response is controlled by anti-inflammatoriy molecules (IL-1 receptor antagonist [IL-1 ra], transforming growth factor-beta [TGF-ß], interleukins 4, 6, 10, 11 and 13), and the specific receptors for IL-1, TNF, and interleukin 18. In physiological conditions, all these molecules serve as immunemodulators and as a result they limit the potentially harmful effect of the inflammatory reaction. However, in pathological conditions anti-inflammatory response can be insufficient in order to counteract the inflammatory activity or, on the contrary, can be excesive with immune system inhibition so that fails to help the host faced with the infection. From the start of sepsis symptomatology until the day 28, and when clinical disturbances of SIRS are already gone, the global balance among the pro- inflammatory and anti-inflammatory molecules studied aims at a very important increase of anti-inflammatory molecules. The role of TNF-α and IL-1 ß in sepsis seems to be that of triggering factors, but subsequently both lack of pathogenic role. sTNFR-I, sTNFR-II and IL-1 ar have great prognostic value and their levels are related to the development of MODS and to the failure of every organ system. Higher levels of IL-10 and TFR-ß are also related to mortality, although in late phases. Future therapeutic interventions should take into account the fact that sepsis is a dynamic process

[Effect of immunomodulator AM3 on the exacerbations in patients with chronic bronchitis: a systematic review of controlled trials]. / Efecto del inmunomodulador AM3 sobre las agudizaciones en enfermos con bronquitis crónica: una revisión sistemática de estudios controlados.

OBJECTIVE: Analyze the effect of AM3, an oral immunomodulator, on the exacerbations and on the use of antibiotics in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic search of controlled clinical trials that used AM3 in some treatment group and that included data on the clinical effects of this drug on patients with COPD. SELECTED VARIABLES: Nine studies were detected in which the clinical effectiveness of AM3 was evaluated in relation to the number of infectious exacerbations, their length, and the length of the antibiotic treatment used. RESULTS: In comparison with placebo group, the average number of excaerbations suffered by the patients treated with AM3 declined significantly in 0.31 units (p < 0.001; 95% confidence interval: 0.20-0.42), without heterogeneity among the different studies (Q = 6.62; p > 0.43). With regard to the average length of the exacerbations and the average length of the antibiotic treatment used for the exacerbations, both variables declined significantly in the group treated with AM3 (3.10 days, p < 0.001, and 8.07 days, p < 0.001, respectively) but this positive effect could not be confirmed because trials were close to heterogeneity. CONCLUSIONS: The results of this systematic review show that AM3 has a clinical effect in the prevention of exacerbations of COPD patients because reduces significantly their number. This could be related to a slowing in the progression of the deterioration in the respiratory function with a potential impact on the quality of life of the patients. Furthermore, these data imply a positive therapeutic result and a possible decline in development of bacterial resistances secondary to the frequent and indiscriminate use of antibiotics in these patients.

[Urinary excretion of cytokines in bladder carcinoma]. / Excreción de citocinas urinarias en los carcinomas vesicales.

OBJECTIVE: Analysis of the urinary excretion of cytokines in vesical carcinoma. MATERIAL AND METHOD: The study includes the results obtained in the quantification of several interleukins (IL-1, IL-2, IL-4, IL-6, INF-gamma and TNF-alpha) in urine samples corresponding to 60 patients with transitional cell carcinoma (TCC) with vesical location (40 surface and 20 infiltrant). Concurrently, 40 healthy donors and 20 patients with urinary tract infections were studied. Determination of the various cytokines was done with ELISA enzyme-linked immunoassays. RESULTS: The results obtained in the study show that: a) urinary concentrations of IL-1, IL-2, IL-6, TNF- and INF- in surface TCC, are similar to those found in healthy subjects; b) levels of the mentioned cytokines are significantly higher in patients with urinary infections; c) in patients with infiltrant TCC, IL-6 urinary concentration is significantly higher than in those with S-TCC; d) urinary IL-4 levels show no difference between the various groups under study. CONCLUSION: From all the above it is concluded that there is a large diversity in the excretion of urinary cytokines from the vesical urothelium based on antigenic stimulation (bacterial or tumoral) to which it has been exposed and the tumoral stage, and that baseline determination of IL-6 urine level in patients with vesical TCC could have some prognostic influence.