By using mice genomically lacking IFN-γR, IL-12, perforin, and recombination-activating gene-1 (RAG-1), we analyzed the regulation and importance of IFN-γ in the control of infection with Chlamydia pneumoniae. IL-12 participates in resistance of mice to C. pneumoniae, probably by regulating the protective levels of IFN-γ mRNA. In turn, IFN-γ is necessary for the increased IL-12p40 mRNA accumulation that occurs in lungs during infection with C. pneumoniae, suggesting a positive feedback regulation between these two cytokines. In experiments including RAG-1−/−/IFN-γR−/− mice we showed that IFN-γ produced by innate cells controls the bacterial load and is necessary for the increased accumulation of transcripts for enzymes controlling high output NO release (inducible NO synthase), superoxide production (gp-91 NADPH oxidase), and catalyzis of tryptophan (indoleamine 2,3-dioxygenase (IDO)), mechanisms probably related to bacterial killing. Adaptive immune reponses diminish the levels of IFN-γ and IL-12 mRNA and thereby the levels of inducible NO synthase, IDO, and gp91 NADPH oxidase trancripts. By using RAG-1−/−/perforin−/− mice, we excluded the overt participation of NK cell cytotoxicity in the control of C. pneumoniae. However, NK cells and probably other innate immune cells release IFN-γ during the bacterial infection.

Natural killer (NK) cells can spontaneously lyse certain virally infected and transformed cells. However, early in immune responses NK cells are further activated and recruited to tissue sites where they perform effector functions. This process is dependent on cytokines, but it is unclear if it is regulated by NK cell recognition of susceptible target cells. We show here that infiltration of activated NK cells into the peritoneal cavity in response to tumor cells is controlled by the tumor major histocompatibility complex (MHC) class I phenotype. Tumor cells lacking appropriate MHC class I expression induced NK cell infiltration, cytotoxic activation, and induction of transcription of interferon γ in NK cells. The induction of these responses was inhibited by restoration of tumor cell MHC class I expression. The NK cells responding to MHC class I–deficient tumor cells were ∼10 times as active as endogenous NK cells on a per cell basis. Although these effector cells showed a typical NK specificity in that they preferentially killed MHC class I–deficient cells, this specificity was even more distinct during induction of the intraperitoneal response. Observations are discussed in relation to a possible adaptive component of the NK response, i.e., recruitment/activation in response to challenges that only NK cells are able to neutralize.

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.

Role of IFN-mice were unable to activate the cytotoxic response but produced IFN-g , and were not more susceptible than controls. IL-12 -/-mice were extremely susceptible and failed to produce T cell-derived IFN-g and nitric oxide (NO), although NK cytotoxicity was induced. The results indicate that IL-12 protects against T. cruzi by initiating T cell-mediated production of IFN-g , but that endogenous IFN-a / b and NK cell cytotoxicity are not of major importance in defence.

Individuals with atrophic gastritis (AG), especially atrophic body gastritis (ABG), are at increased risk of developing gastric cancer. Serum concentrations of pepsinogens (PG) have been proposed as markers for ABG. The aim of this study was to determine the risk factors for AG and ABG and the potential of using serum PG concentrations to detect ABG in a dyspeptic population in Costa Rica, which is one of the countries with the highest incidence and mortality rates of gastric cancer in the world. Seven biopsy specimens, a fasting blood sample and a questionnaire concerning sociodemographic factors were obtained from 501 consecutive dyspeptic patients. The serum PGI level and the PGI/PGII ratios were significantly lower in patients with ABG than in other groups (P<0.000). A cut-off point of 3.4 led to a sensitivity of 91.2% in identifying ABG, a negative predictive value of 98.1%, but a positive predictive value of only 11.2%. Helicobacter pylori were present in 93% of the patients and all those with peptic ulcers were positive. AG was associated with increased age, lower body mass index, high alcohol intake and low fruit consumption. ABG was associated with age, alcohol consumption and PGI/PGII<3.4. In dyspeptic patients with a high prevalence of H. pylori infection, serum PG levels provide an assessment of ABG but it is necessary to introduce other serological and genetic markers in order to achieve a better specificity. Those markers could be serum antibodies to H. pylori-CagA, cytokine gene polymorphisms or others.