Citocinas e imunomodulação: novos avanços no tratamento das pancreatites

Inflammation is the principal feature of pancreatitis. Cytokines play a fundamental role in local and systemic inflammation, mediating tissue damage and orchestrating the ultimate results. This paper reviews the role of cytokines in acute and chronic pancreatitis, describing the different approaches of this subject and their methodological limitations. We also emphasize the new therapeutical modalities for pancreatitis, based in immunomodulation.As pancreatites se caracterizam por intenso processo inflamatório. A ativação de citocinas determina ou modula os principais mecanismos de lesão tissular local e à distância, participando dos danos que caracterizam as formas agudas ou crônicas de pancreatite. O trabalho faz uma revisão dos aspectos referentes à participação das citocinas na fisiopatologia das pancreatites, descrevendo de forma crítica as abordagens metodológicas que permitiram o seu estudo e apontando as novas modalidades de tratamento, com base na imunomodulação das citocinas

A pancreatite aguda na visão do imunologista

The acute pancreatitis is an inflammatory process of the pancreas, resulting from the action of enzymes activated inappropriately,causing swelling, bleeding and even pancreatic necrosis and peripancreática. The acinar cells in the pancreas and stellar cellspancreatic has been the study as participants in shaping the inflammatory process along with other inflammatory cells. Severalcytokines are released during pancreatitis, and thus, the local inflammatory process initially, may have an important systemicimpact, and the patient may present hypovolemia, involvement of multiple organs and systems and the possibility of death. Theclinical condition of pancreatitis as mild or severe depends on the length of the process and the complications that may arise.A pancreatite aguda é um processo inflamatório do pâncreas, decorrente da ação de enzimas inadequadamente ativadas,que causam edema, hemorragia e até necrose pancreática e peripancreática. As células acinares presentes no pâncreasassim como as células estelares pancreáticas tem sido alvo de estudo como participantes na formação do processoinflamatório juntamente com outras células inflamatórias. Diversas citocinas são liberadas durante a pancreatite, e assim,o processo inflamatório inicialmente local, pode ter uma repercussão sistêmica importante, e o paciente poderá apresentarhipovolemia, comprometimento de múltiplos órgãos e sistemas e possibilidade de óbito. A condição clinica da pancreatitena forma leve ou grave dependerá da extensão do processo e das complicações que podem advir

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.Fapesb [SUS0001/2011]Fapesp [10/10.549-1

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Polimorfismo do HLA de classe II em populações brasileiras

The investigation of the distribution and frequency of HLA (Human Leukocyte Antigen) genes in presumably healthy populations is important to evaluate the participation of these genes in the susceptibility and protection against diseases, to evaluate the genetic origins of populations and to aid in the practice of transplantations. The advances in molecular biology has allowed a better understanding of this system. In addition, information about the HLA class II molecules, such as their mechanism of action, function, and genetic polymorphism, granted their use as markers for ethnic composition of a population and even of individual distinction. The HLA class II genes appear to be associated with some racial/ethnic groups more than others. By using these genetic characteristics, it may be possible to demonstrate, for example, the degree of admixture of Caucasians, Africans and Amerindians that marks in a significant way the origin of the Brazilian population. It also clarifies some aspects of the ancestry of this population and helps the performance of population studies with the objectives to obtain information related to the history and formation features, migration and composition of theses groups, in conformity with local particularities. The relevance of this theme is the frequency of HLA class II antigens, alleles and haplotypes in the Brazilian populations.A investigação da distribuição e freqüência dos genes HLA (Human Leukocyte Antigens) em populações presumivelmente saudáveis é importante para avaliar a participação desses genes na susceptibilidade e proteção a doenças, para avaliar a origem genética das populações e para auxiliar na realização de transplantes. Os avanços na biologia molecular têm permitido um melhor entendimento desse sistema. Além disso, informações sobre as moléculas HLA de classe II, tais como seu mecanismo de ação, função e polimorfismo genético têm colocado esse sistema como marcador da composição das populações. Os genes HLA de classe II parecem ser associados a alguns grupos étnico-raciais mais que a outros. Usando essas características genéticas, é possível demonstrar, por exemplo, o grau de mistura de caucasianos, africanos e ameríndios que contribuem, de modo significante, para a origem da população brasileira, bem como esclarecer alguns aspectos da ancestralidade dessas populações, o que ajuda na realização de estudos populacionais com o objetivo de obter informações sobre a história, formação, migração e composição de grupos populacionais de acordo com suas peculiaridades locais. Esse tema assume relevância em virtude da freqüência dos antígenos, alelos e haplótipos HLA de classe II na população brasileira