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Biomedical subjects

Z Xing

Publications and source records attributed to Z Xing.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interleukin 10 gene transfer prevents experimental colitis in rats.

BACKGROUND: The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results. AIMS: To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats. METHODS: Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations. RESULTS: Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect. CONCLUSIONS: Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.

Adenoviridae↗
PubMed2000

Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and airway hyperresponsiveness in IL-4-deficient mice.

We studied the role of interleukin (IL)-4, IL-5, and allergen-specific immunoglobulin (Ig) E in the development of allergen-induced sensitization, airway inflammation, and airway hy-perresponsiveness (AHR). Normal, IL-4-, and IL-5-deficient C57BL/6 mice were sensitized intraperitoneally to ovalbumin (OVA) and repeatedly challenged with OVA via the airways. After allergen sensitization and airway challenge, normal and IL-5-deficient, but not IL-4-deficient, mice developed increased serum levels of total and antigen-specific IgE levels and increased IL-4 production in the lung tissue compared with nonsensitized control mice. Only normal mice showed significantly increased IL-5 production in the lung tissue and an eosinophilic infiltration of the peribronchial regions of the airways, whereas both IL-4- and IL-5-deficient mice had little or no IL-5 production and no significant eosinophilic airway inflammation. Associated with the inflammatory responses in the lung, only normal mice developed increased airway responsiveness to methacholine after sensitization and airway challenge; in both IL-4- and IL-5-deficient mice, airway responsiveness was similar to that in nonsensitized control mice. Reconstitution of sensitized, IL-4-deficient mice before allergen airway challenge with IL-5, but not with allergen-specific IgE, restored eosinophilic airway inflammation and the development of AHR. These data demonstrate the importance of IL-4 for allergen-driven airway sensitization and that IL-5, but not allergen-specific IgE, is required for development of eosinophilic airway inflammation and AHR after this mode of sensitization and challenge.

Animals↗
PubMed2000

Current understanding of macrophage type 1 cytokine responses during intracellular infections.

Macrophages are important effector cells in cell-mediated immunity against intracellular infection. Among cytokines that macrophages are able to release are IL-12 and TNF alpha. IL-12 is a critical linker between the innate and adaptive cell-mediated immunity, capable of Th1 differentiation and IFN gamma release by T and NK cells. IFN gamma is critically required for the activation of macrophage bactericidal activities. Recently emerging evidence suggests that macrophages are able to release not only IL-12 and TNF alpha but also IFN gamma. However, the mechanisms that control the release of each of these type 1 cytokines in macrophages appear different. While macrophages release TNF alpha in an indiscriminate and IL-12-independent way, the release of IL-12, particularly bioactive IL-12 p70, and IFN gamma is under tight control. We are just beginning to understand what controls the release of IL-12 p70, a question of fundamental importance to understanding the mechanisms underlying the initiation of cell-mediated immunity. Our recent findings have shed more insights into the regulatory mechanisms of macrophage IFN gamma responses. It has become evident that IL-12 is required not only for Th1 differentiation but also for IFN gamma responses by both T cells and macrophages during intracellular infection. In this overview, we have discussed about the current understanding of the regulation of macrophage type 1 cytokine responses during intracellular infection, based upon the recent findings from us and others.

Animals↗
PubMed2000

Consideration of cytokines as therapeutics agents or targets.

There has been an explosion of our knowledge in cytokine biology in the last decade. Such knowledge is being quickly translated into the identification of etiologies and improved prophylaxis and therapy of disease. While cytokines have the potential to be used as therapeutics or immune adjuvants for certain diseases, they may also be culprits as therapeutic targets in other diseases. This review article serves, as an introduction to the other five articles in this thematic issue each of which has a specific focus on the frontier of cytokine therapeutic biology. This review contains sections dealing with general cytokine properties, cytokine classifications, human conditions caused by cytokine under-expression and over-expression, Th1 and Th2 paradigm, cytokine therapy for acute/chronic inflammatory conditions, cytokine therapy for infectious diseases, and cytokine therapy for cancer.

Animals↗
PubMed2000

Role of IL-12 in macrophage activation during intracellular infection: IL-12 and mycobacteria synergistically release TNF-alpha and nitric oxide from macrophages via IFN-gamma induction.

IL-12 is believed to play an important role in cell-mediated immunity against intracellular infection primarily by acting on T and NK cells. Recent evidence has suggested, however, that IL-12 has broader cellular targets than previously thought. In this study, we examined the role of IL-12 in macrophage TNF-alpha and nitric oxide (NO) release by using an in vitro model of intracellular infection. IL-12 alone released relatively little TNF-alpha and NO, whereas live mycobacteria alone released TNF-alpha markedly but little NO from murine alveolar macrophages. However, IL-12 and mycobacteria together enhanced TNF-alpha and NO release synergistically. Because IL-12 and mycobacteria also released IFN-gamma from macrophages synergistically, and exogenous IFN-gamma with mycobacteria enhanced TNF-alpha and NO release synergistically, we examined the role of endogenous IFN-gamma in IL-12/mycobacteria-stimulated macrophage activation. Using macrophages from mice deficient in IFN-gamma, we found that IL-12/mycobacteria-enhanced macrophage TNF-alpha and NO release was mediated through endogenous IFN-gamma. We further demonstrated that IFN-gamma and mycobacteria together had a selective effect on macrophage cytokine release because they released TNF-alpha synergistically but not macrophage chemotactic protein-1 (MCP-1). These findings reveal that IL-12 can activate macrophages potently during intracellular infection, and this activating effect is mediated primarily through its effect on macrophage IFN-gamma release.

Animals↗
PubMed2000

[Annular constriction of popliteal vein for treating severe venous insufficiency].

OBJECTIVE: To study the mechanism and therapeutic effects of annular constriction for severe venous insufficiency of legs. METHODS: Annular constriction of popliteal vein was performed by Gore-Tex vascular graft in 82 patients. Among them, 78 patients had deep venous valve insufficiency of legs (III, IV degree), 2 postphlebitic syndrome, and 2 valve absence of deep vein. Under normal respiration and breath holding, venous pressure was measured at the proximal and distal part from the constricting site. RESULTS: Great difference was noted in the venous pressure between the proximal and distal part from the constricting site. The pressure was (9.4 +/- 4.5) mm Hg, (41.2 +/- 28.1) mm Hg at calm and (32.4 +/- 16.2) mm Hg, (41.2 +/- 28.1)mm Hg at breath holding (P < 0.01). Symptoms disappeared or released after operation. Ulcer healed in all patients. Venous pressure decreased by over 60%. Pressure recovery time was over 22 seconds. There was no reflux distal to the constricting site. Deep venous angiography and color Doppler showed an effect similar to venous valve. CONCLUSION: Annular constriction is effective in treating severe venous insufficiency of legs.

Constriction↗
PubMed2000

[Primary study on immunologic effect of live attenuated hepatitis A vaccine (H2 strain) after booster dose].

OBJECTIVE: To study the immunologic effect of live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50)) after booster and to compare with the results of 1 dose live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50)). METHODS: 42 susceptibles with negative anti - HAV were selected in Zhengding, Hebei province. Each subject received 3 doses live attenuated hepatitis A vaccine at 0, 2, 6 months and was bled at 1, 2, 6, 7, 9, 12 months after vaccination. RESULTS: The seroconversion rate at 1 month after the first dose was 81.4% and reached 100% after the second dose. GMT arrived the peak 2,739 mIU/ml at one month after the third dose, before stared declining. The seroconversion rate kept 100% at 12 months after the first dose, but GMT decreased to 979 mIU/ml. CONCLUSION: The first dose worked as the base of boostering. A booster dose of live attenuated hepatitis A vaccine could induce secondary immune response well. The immunologic effect after booster dose could match the effect with inactivated vaccine and was better than the results of 1 dose live attenuated hepatitis A vaccine. The program seemed to be useful to the protective effect and the immuno - persistence.

Child↗
PubMed2000

[The outcome of 1268 cases of endoscopic sinus surgery].

OBJECTIVE: To evaluate the curative effect of endoscopic sinus surgery (ESS). METHODS: One thousand two hundred and sixty-eight cases with chronic sinusitis and nasal polyps undergone ESS from 1989 to 1997 were appraised with the standard criteria (Chinese ENT Association, 1997). There were 366 cases(28.9%) in type 1, 646 cases(50.9%) in type 2 and 256 cases(20.2%) in type 3. One thousand two hundred and sixty-two cases underwent ESS under intranasal local anesthesia and sedation; 182 cases underwent submucous resection of nasal septum or septoplasty. Long-term follow-up was performed at 9 to 42 months(mean = 15 months). RESULTS: The results showed that cure rate was 93.7% for type 1, 81.6% for type 2 and 68.4% for type 3. There was significant difference in cure rate among different types (P < 0.01). Complication of ESS in 1,268 cases occurred in 2.3%. CONCLUSION: ESS is efficacy and safe in the treatment of nasal polyps and chronic sinusitis. The cure result is directly related to the types of the disease.

Adult↗
PubMed1999

Adenoviral-mediated gene transfer of interleukin-6 in rat lung enhances antiviral immunoglobulin A and G responses in distinct tissue compartments.

The effect of IL-6 transgene expression following lung gene transfer on anti-adenovirus humoral responses of immunoglobulin (Ig) G and A both in the lung and peripheral blood was investigated. Lung infection by a control adenovirus caused an increased level of circulating anti-adenoviral IgG antibodies. However, the magnitude of this response was many times higher in the peripheral blood of rats receiving an adenovirus engineered to express IL-6 transgene. In comparison, much lower levels of anti-adenoviral IgG were detected in the bronchoalveolar fluids of rats receiving either virus. In contrast, there was no detectable level of anti-adenoviral IgA in the peripheral blood in any cases, yet significantly detectable levels of anti-adenoviral IgA were measured in the lung. The levels of this IgA were much higher in the lung of rats expressing IL-6 than in the lung of control animals (15 times higher by day 14). Our findings thus provide evidence that IL-6 plays a significant role in enhancing specific airways mucosal IgA and systemic IgG responses during local lung viral infection, and provide the rationale for using IL-6 locally at mucosa sites as an immune adjuvant for antiviral vaccination program.

Adenoviridae↗
PubMed1999

Replication-defective adenovirus infection reduces Helicobacter felis colonization in the mouse in a gamma interferon- and interleukin-12-dependent manner.

Helicobacter infection leads to chronic inflammation of the stomach. Although the infection persists in spite of an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against infection and even eliminate established infection. These vaccines are thought to induce a Th2 immune response, counterbalancing the Th1 response seen with natural infections. As a prelude to using adenovirus vectors carrying cytokine genes to modulate the immune response to established Helicobacter felis infection, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected with H. felis (8 to 10 weeks) received intramuscular injections of RDA. The effect of RDA on the severity of H. felis colonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease in H. felis colonization without significantly altering the associated inflammation. RDA did not alter the H. felis-specific immunoglobulin G1 (IgG1), IgG2a, and IgA responses in the serum but was associated with an increase in gamma interferon (IFN-gamma)-producing CD8(+) spleen cells. To determine if IFN-gamma or Th1 cytokines were involved in the response to RDA, we examined RDA treatment of H. felis infection in mice lacking either IFN-gamma or interleukin-12 (IL-12). RDA failed to alter H. felis colonization in either of these two mouse strains. Thus, viral infection of mice chronically infected with H. felis led to a significant decrease in H. felis colonization in an IFN-gamma- and IL-12-dependent manner. These results demonstrate that Th1 responses associated with systemic viral infection can influence an established H. felis infection.

Adenoviridae Infections↗
PubMed1999

Regulation of allergic mucosal sensitization by interleukin-12 gene transfer to the airway.

Expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in the airway allows allergic sensitization to ovalbumin (OVA) in an experimental protocol that others have shown to induce inhalation tolerance. The ensuing response is characterized by T helper (Th)2 cytokines, marked eosinophilia in the bronchoalveolar lavage fluid (BALF) and the tissue, and goblet-cell hyperplasia. These findings, which underscore the importance of the airway microenvironment in the development of immune responses to airborne antigens, prompted us to investigate whether a Type 1 polarized cytokine milieu in the airway would modulate the allergic sensitization. To this end, we concurrently expressed GM-CSF and interleukin (IL)-12 in the airway, using an adenovirus-mediated gene transfer approach. Coexpression of IL-12 did not prevent the development of an antigen-specific immune inflammatory response, but altered its phenotype. Whereas a similar total cell number was observed in the BALF, airway eosinophilia was abrogated. Histologic evaluation of the tissue corroborated the findings in the BALF and demonstrated that IL-12 coexpression prevented goblet-cell hyperplasia. Expression of IL-12 decreased IL-4 and IL-5 content in the BALF by about 80 and 95%, respectively, and IL-5 in the serum by approximately 80%. In contrast, interferon (IFN)-gamma was increased in both BALF and serum. Similarly, we observed a Th2/Th1 shift in OVA-specific cytokine production in vitro. Recall challenge with OVA in vivo after resolution of the initial inflammatory response demonstrated that the effect of IL-12 was persistent. IL-12-mediated inhibition of airway eosinophilia was mainly IFN-gamma-independent, whereas inhibition of OVA-specific IgE synthesis was IFN-gamma-dependent. Our data underscore the importance of the airway microenvironment in the elicitation of immune responses to environmental antigens.

Adenoviridae↗
PubMed1999

Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice.

The objective of this study was to investigate the effect of airway gene transfer of interleukin (IL)-10, a cytokine with potent anti-inflammatory and immunoregulatory activities, on allergic mucosal sensitization. We used a recently described murine model that involves repeated exposures to aerosolized ovalbumin (OVA), daily for 10 d, in the context of granulocyte macrophage colony-stimulating factor (GM-CSF) expression in the airway environment achieved by intranasal delivery of a replication-deficient adenovirus carrying the GM-CSF transgene. The resulting inflammatory response was characterized by a T-helper 2 cytokine profile and marked airway eosinophilia. After complete resolution of the inflammatory response (Day 28), a single exposure to OVA reconstituted airway eosinophilia and induced airway hyperresponsiveness. We show that concurrent expression of IL-10 inhibited GM-CSF-driven OVA-specific inflammation in a dose-dependent manner. Specifically, IL-10 decreased the number of mononuclear cells, neutrophils, and eosinophils in the bronchoalveolar lavage fluid (BALF). Histologic evaluation of the tissue corroborated the findings in the BALF. Concurrent expression of IL-10 at the time of mucosal sensitization abrogated both the cellular and physiologic recall responses in vivo. Studies in interferon (IFN)-gamma knockout mice demonstrated that prevention of airway eosinophilia by IL-10 was IFN-gamma-independent and that expression of IL-10 was associated with decreased levels of IL-4, IL-5, and tumor necrosis factor-alpha in the BALF. Flow cytometric analysis of dispersed lung cells showed that expression of IL-10 in the airway reduced the absolute number of Class II major histocompatibility complex (MHC)(+)/CD11c(+) (dendritic cells) and Class II MHC(+)/Mac-1(bright) (macrophages) cells expressing the costimulatory molecules B7.1 and B7.2 by 30%. However, IL-10 coexpression did not prevent expansion of CD4 and CD8 T cells or expression of the early activation marker CD69 on T cells. Thus, airway gene transfer of IL-10 altered the immune response to OVA in a way that resulted in inhibition of airway inflammation. These findings suggest that development of an immunoregulatory strategy based on IL-10, alone or in combination with GM-CSF, warrants further consideration.

Adenoviridae↗
PubMed1999

Macrophages are a significant source of type 1 cytokines during mycobacterial infection.

T-helper 1 (Th1) cells are believed to be the major producer of the type 1 cytokine interferon-gamma (IFN-gamma) in cell-mediated immunity against intracellular infection. We have investigated the ability of macrophages to release type 1 cytokines and their regulatory mechanisms using both in vivo and in vitro models of pulmonary mycobacterial infection. During pulmonary infection by live Mycobacterium bovis bacilli Calmette-Guérin (BCG) in wild-type mice, lung macrophages released interleukin-12 (IL-12), IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), and expressed surface activation markers. However, macrophages in infected IL-12(-/-) mice released TNF-alpha but not IFN-gamma and lacked surface activation makers. In freshly isolated lung macrophages from naive IL-2(-/-) mice, mycobacteria alone released TNF-alpha but not IFN-gamma, whereas exogenously added IL-12 alone released a minimum of IFN-gamma. However, these macrophages released large quantities of IFN-gamma upon stimulation with both mycobacteria and IL-12. In contrast, mycobacteria and exogenous IFN-gamma released only a minimum of endogenous IFN-gamma. Endogenous IL-18 (IFN-gamma-inducing factor) played little role in IFN-gamma responses by macrophages stimulated by mycobacteria and IL-12. Our data reveal that macrophages are a significant source of type 1 cytokines during mycobacterial infection and that both IL-12 and intracellular pathogens are required for the release of IFN-gamma but not TNF-alpha. These findings suggest that macrophages regulate cell-mediated immunity by releasing not only IL-12 and TNF-alpha but also IFN-gamma and that full activation of IFN-gamma response in macrophages is tightly regulated.

Animals↗
PubMed1999

Cytokines and pulmonary inflammatory and immune diseases.

Cytokines are important soluble signalling molecules that dictate and coordinate inflammatory and immune responses. Further understanding the role of cytokines in the pathobiologic mechanisms of pulmonary inflammatory and immune diseases holds the key to the development of effective prophylactic and therapeutic strategies. In the last several years, the use of models of human pulmonary diseases established either in normal adult animals, mice deficient for a given immune cell type or cytokine, or mice engineered to overexpress a given cytokine, has remarkably facilitated our understanding of the mechanisms operating in human disease. Cytokines that are involved in pulmonary inflammatory and immune conditions may be generally divided into groups of pro-inflammatory, anti-inflammatory and growth-stimulatory cytokines. While pro-inflammatory cytokines can be detrimental under such severe conditions as endotoxemia and fibrosis, they are required in host resistance against infectious agents. Anti-inflammatory cytokines play an important role in controlling the extent of tissue inflammatory/immune responses. Overexpression of growth-stimulatory cytokines are often directly associated with tissue fibrotic responses. In this review, the findings attained from experimental models by us and others were discussed with emphasis on cellular and histopathologic alterations, cytokine-mediated molecular mechanisms and the prospects of cytokine-based therapeutic strategies. Due to the restrict space, we chose to focus only on models for endotoxic lung, endotoxemia, acute pulmonary infections by extracellular Gram-negative bacteria, chronic pulmonary infections by intracellular myco-bacteria, allergic airways inflammation and pulmonary fibrosis.

Animals↗
PubMed1998

GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice.

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.

Adenoviruses, Human↗
PubMed1998

Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia.

IL-5 is induced locally in the lung and systemically in the circulation during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5(+/+) counterparts, IL-5(-/-) mice lacked an IL-5 response both in the lung and peripheral blood, yet they released similar amounts of IL-4, eotaxin, and MIP-1alpha in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5(+/+) mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5(-/-) mice led to raised levels of IL-5 compartmentalized to the circulation and completely reconstituted airways eosinophilia upon OVA challenge, which was associated with reconstitution of eosinophilia in the bone marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. In contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compartmentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5(-/-) mice upon OVA-challenge, which was associated with a lack of eosinophilic responses in bone marrow and peripheral blood. Our findings thus provide unequivocal evidence that circulating but not local lung IL-5 is critically required for the development of allergic airways eosinophilia. These findings also provide the rationale for developing strategies to target circulating IL-5 and/or its receptors in bone marrow to effectively control asthmatic airways eosinophilia.

Adenoviridae↗
PubMed1998

Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune protection during pulmonary infection by Mycobacterium bovis bacille Calmette-Guérin in IL-12-deficient mice.

Understanding of key cytokines and the nature of protective immune responses in pulmonary mycobacterial diseases remains a task of paramount importance. In this study, both wild-type (wt) and IL-12-deficient (IL-12(-/-)) mice were infected by airways inoculation of live Mycobacterium bovis bacille Calmette-Guérin (BCG). The type 1 cytokines IL-12, IFN-gamma, and TNF-alpha, but not the type 2 cytokines IL-4 and granulocyte macrophage (GM)-CSF, markedly increased in the lung and peripheral blood of wt mice postinfection, which resulted in the development of intense granulomatous responses and the effective control of mycobacterial infection in the lung. In contrast, IL-12(-/-) mice demonstrated a lack of both types 1 and 2 cytokines in the lung and blood and a severely impaired tissue immune-inflammatory response lacking not only macrophages and neutrophils but CD4 and CD8 T cells and NK cells in the lung throughout the entire course of study. Total lung mononuclear cells isolated from these mice, in contrast to wt mice, had an impaired recall immune response to Ag challenge in vitro. These impaired responses resulted in an uncontrolled local growth and systemic spread of bacilli. Our findings reveal that IL-12 plays an irreplaceable role in the initiation of Th1 responses, and the loss of its function cannot be compensated for by alternative mechanisms in the lung. This cytokine, together with IFN-gamma and TNF-alpha, and granulomatous inflammation are critically required for the effective control of pulmonary mycobacterial infection. Our results also indicate that the absence of type 1 cytokines does not necessarily favor a Th2 response.

Animals↗