The Impact of Sleeve Gastrectomy on Inflammatory Markers and Immune Response: A Study of Cytokine Changes, Weight Loss, and Insulin Resistance

Obesity is a major global health concern and is closely linked to a variety of chronic conditions, including type 2 diabetes, cardiovascular diseases, and metabolic syndrome. One of the underlying mechanisms connecting obesity to these conditions is chronic low-grade systemic inflammation, which is driven by an excess accumulation of fat in the body. Adipose tissue releases several inflammatory mediators, such as tumor necrosis factor and interleukins, which are found in elevated levels in obese individuals and contribute to immune system imbalance and metabolic dysfunction [1].

Lifestyle modification, including diet and physical activity, is typically the first approach to managing obesity. While this approach can yield some benefits, long-term success is often limited due to weight regain [1]. As a result, bariatric surgery has emerged as the most effective treatment for achieving significant and sustained weight loss. Among various surgical options, sleeve gastrectomy (SG) has become the most frequently performed procedure worldwide and in Iraq. It involves the surgical removal of about 80% of the stomach, creating a narrow, tube-like stomach that limits food intake and leads to reduced appetite and weight loss [3].

Compared to non-surgical interventions, SG produces more substantial weight loss but also induces significant physiological changes. These include alterations in hormone levels, nutrient absorption, and gut microbiota, all of which can influence the body’s immune and inflammatory responses [4]. Some patients may experience post-surgical complications related to these changes, such as hormonal imbalances or nutritional deficiencies. In rare cases, individuals with genetic susceptibility may develop neurological conditions like myelopathy due to increased inflammatory signaling and disruption of the gut-brain axis [5,6].

One important benefit of bariatric surgery is its ability to improve insulin resistance, a condition commonly associated with obesity-related inflammation. Proinflammatory chemicals not only interfere with insulin function but also affect vascular reactivity, clotting, and nerve activity [7]. Although various studies have explored changes in blood cytokines before and after bariatric surgery, many focus on limited markers or small patient groups, making it difficult to draw broad conclusions [8].

Persistent inflammation and immune dysregulation play a critical role in the worsening of metabolic dysfunction in obesity [9]. Despite this, there is still a lack of comprehensive research evaluating how a range of inflammatory markers respond to bariatric procedures, particularly in Middle Eastern populations. In Iraq, where obesity is increasingly common, there is a need for localized data to guide clinical decisions and understand the specific outcomes of SG in this setting.

This study aims to address this gap by assessing changes in inflammatory markers, immune response, and metabolic parameters in obese Iraqi patients undergoing sleeve gastrectomy. It seeks to provide valuable insight into the health benefits of SG and its potential role in managing obesity-related inflammation and insulin resistance.

Study Design and Participants

This cross-sectional study was conducted between October 2023 and October 2024 at a private medical clinic located in Al-Harthia, Baghdad. The study included patients who were scheduled to undergo bariatric surgery, specifically either vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Eligible participants were adults with obesity, defined as a body mass index (BMI) greater than 40 kg/m², or greater than 35 kg/m² in the presence of one or more obesity-related health conditions such as hypertension or type 2 diabetes.

Patients who had undergone previous weight loss surgery were excluded from the study. Additionally, lean individuals (BMI ≤ 26 kg/m²) with no history of diabetes or cardiovascular disease were not included. A total of 40 patients were selected based on age, sex, and ethnicity to ensure a balanced group. All patients agreed to participate in the study and attended follow-up assessments at three and six months after surgery.

Data Collection

During clinic visits, data were collected on patient demographics, weight, and height. BMI was calculated by dividing weight in kilograms by the square of height in meters (kg/m²). Blood samples were collected in the morning after an overnight fast. These samples were processed to separate the serum, which was then frozen at –80°C until further analysis.

Laboratory Measurements

Fasting blood glucose levels were measured from the serum samples. Insulin levels were determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Millipore Human Insulin, Billerica, MA, USA). Insulin resistance was calculated using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) method (28), which estimates how well the body uses insulin based on fasting glucose and insulin levels.

To evaluate the immune and inflammatory responses, several cytokines were measured using ELISA kits (Jiancheng, Nanjing, China). These included interleukin-1 beta (IL-1β), interferon-alpha (IFN-α), interferon-gamma (IFN-γ), interleukin-12 (IL-12), interleukin-23 (IL-23), interleukin-33 (IL-33), and monocyte chemoattractant protein-1 (MCP-1). These markers were chosen for their known roles in inflammation and metabolic regulation. C-reactive protein (CRP), an indicator of inflammation, was measured using an immunoturbidimetric method at a wavelength of 570 nm with a Roche Cobas Mira chemistry analyzer (Roche Cobas 8000, Germany).

Statistical Analysis

Data were summarized using means and standard error of the mean (SEM) for continuous variables, and percentages for categorical variables. Normal distribution of continuous variables was verified before analysis. Cytokine levels were logarithmically transformed to adjust for skewed data and allow for more accurate comparisons. Group comparisons, including preoperative and postoperative data at 3 and 6 months, were conducted using Student’s t-test and one-way analysis of variance (ANOVA) for normally distributed variables. A two-tailed p-value of less than 0.05 was considered statistically significant. All statistical analyses were carried out using Stata Statistical Software version 11.0 (StataCorp LP, College Station, TX, USA).

Ethical Considerations

All participants were informed about the nature and purpose of the study and gave written consent before enrollment. Their personal data were kept confidential, and coded identifiers were used in place of names to protect privacy. Participation was entirely voluntary, and patients were free to withdraw at any time without affecting their medical care. Ethical approval was obtained from the appropriate institutional review board, ensuring that all procedures followed standard ethical guidelines.

Participant Characteristics

A total of 40 patients who underwent sleeve gastrectomy were included in the study. They were stratified into three groups based on the time of assessment: prior to surgery, three months postoperatively, and six months postoperatively. The average age of the participants was 48.20±8.15 years. The cohort consisted of 21 males (52.5%) and 19 females (47.5%), as detailed in Table 1.

Reduction in Body Mass Index (BMI)

Significant improvements in BMI were observed following surgery (Table 2). The mean BMI was 43.17±6.01 kg/m² before surgery, which declined to 34.88±5.42 kg/m² at the three-month follow-up and further to 27.64±4.97 kg/m² at six months. Statistical analysis using one-way ANOVA revealed a highly significant reduction across all time points (p<0.001), demonstrating the effectiveness of sleeve gastrectomy in achieving sustained weight loss.

Changes in Metabolic Indicators

The metabolic parameters including fasting blood sugar (FBS), serum insulin, and HOMA-IR are summarized in Table 3. FBS levels decreased significantly from 91.30±7.97 mg/dL preoperatively to 79.72±3.02 mg/dL at three months and 78.25±1.32 mg/dL at six months (P = 0.001). Similarly, insulin concentrations dropped from 12.47±1.32 mU/L before surgery to 6.36±0.79 mU/L and 6.06±0.67 mU/L at the corresponding postoperative intervals (P = 0.001). Despite these improvements, no statistically significant differences were observed in HOMA-IR scores between the groups (P = 0.332), indicating modest change in calculated insulin resistance over time.

Inflammatory Marker: C-Reactive Protein (CRP)

As illustrated in Figure 1, serum high-sensitivity C-reactive protein (hs-CRP) levels exhibited a marked decline post-surgery. Baseline CRP was 0.76±0.11 mg/dL, which reduced to 0.31±0.07 mg/dL at three months and 0.19±0.07 mg/dL at six months. These reductions were statistically significant (P<0.001), indicating a substantial decrease in systemic inflammation. Additionally, a significant difference was detected between the 3-month and 6-month postoperative measurements.

Cytokine Profile and Immune Response

Table 4 presents the concentrations of inflammatory and immune-related cytokines before and after surgery. Levels of IL-1β were significantly higher preoperatively (2.64±0.90 pg/mL) compared to three months (1.39±0.82 pg/mL) and six months postoperatively (0.74±0.13 pg/mL), with statistical significance across all comparisons (P<0.001). Similar trends were observed for IL-12 and IL-23, both of which demonstrated marked and consistent reductions over time (P = 0.001).

Figure 1: Serum high-sensitivity C-reactive protein level in patients before surgery, patients after 3 month of surgery and patients after 6 month of surgery, S: Statistically significant p<0.05

Table 1: Characteristics of patients with gastrectomy

Table 2: Distribution of BMI mean in patients’ groups.

SD: Standard deviation; †: One way ANOVA; HS: Highly-significant at p>0.001

Table 3: Metabolic factors (FBS, Insulin, and HOMA-IR) in patients groups

SD: Standard deviation; †: One way ANOVA; **: Significant at p>0.05

IL-33, IFN-α, and IFN-γ also showed significant declines after surgery (P = 0.015, 0.021, and 0.027, respectively), though the difference between the 3- and 6-month groups was not statistically significant for these markers. MCP-1 levels remained relatively unchanged throughout the study period (P = 0.493), suggesting limited response to surgical intervention for this specific marker.

Graphical Representation of Cytokine Trends

Figure 2 provides a visual overview of changes in immunological parameters across the three time points. Notably, IL-1β, IL-12, and IL-23 demonstrated the most pronounced reductions following surgery, supporting the quantitative findings. The figure underscores the overall downward trend in inflammatory mediators as a result of surgical weight loss.

Figure 2(A,B,C,D, E and D): Serum level of immunological parameters (IL-1B, IL-12 IL-23, IL-33 IFN-α, IFN-γ and Anti-dsDNA) in patients before surgery, patients after 3 month of surgery and patients after 6 month of surgery. NS: Not statistically significant, S: Statistically significant p<0.05

Table 4: Measurements of Immunological parametersin patientsgroups

Test= one way ANOVA; †= *: Significant at p>0.05

Cytokine Correlation Analysis

Correlation analysis among immunological markers is summarized in Table 5. A strong positive correlation was found between IL-1β and IL-23 (r = 0.630, P = 0.001), as well as IL-12 and IL-23 (r = 0.640, P = 0.001), indicating co-regulation. IL-1β also correlated significantly with IL-12 (r = 0.555), IL-33 (r = 0.420), IFN-α (r = 0.331), and IFN-γ (r = 0.460), all with P<0.001. Additionally, IL-12 showed strong correlations with IL-33 (r = 0.486), IFN-α (r = 0.326), and IFN-γ (r = 0.502). Weaker but still significant associations were found between IFN-α and IFN-γ (r = 0.233, P = 0.010). MCP-1 exhibited no meaningful correlation with other cytokines. These results suggest that several cytokines act in a coordinated manner and may jointly reflect the body’s inflammatory response to obesity and its resolution post-surgery.

Table 5: Correlation between Immunological parameters in patients groups

r: Pearson correlation

Obesity continues to be a pressing global health issue, affecting approximately one-third of the world's population and contributing to significant morbidity and mortality [10]. It is a key risk factor for a range of serious conditions including type 2 diabetes, metabolic syndrome, dyslipidemia, cardiovascular disease, and certain types of cancer [11]. The link between obesity and these diseases is largely attributed to chronic low-grade inflammation, sometimes referred to as the "inflammome," which is characterized by increased production of inflammatory cytokines and infiltration of immune cells into fat tissue [12].

The findings from this study demonstrate that sleeve gastrectomy (SG) is effective in reducing body mass index (BMI) and improving metabolic parameters, even within six months of surgery. These results support existing evidence that bariatric surgery is the most effective and durable intervention for treating severe obesity and its associated comorbidities [13]. Although the HOMA-IR values in our study did not change significantly across groups, the notable decrease in fasting insulin and blood glucose suggests improvements in insulin sensitivity and metabolic health.

Laparoscopic sleeve gastrectomy (LSG), the most commonly performed bariatric procedure both globally and in Iraq, involves the surgical removal of approximately 80% of the stomach. This reduces stomach volume to about 100–150 mL and limits food intake while also influencing several hormonal pathways. Research shows that up to 75% of patients undergoing LSG experience full or partial remission of diabetes, accompanied by substantial weight loss and BMI reductions ranging from 8 to 10 kg/m² [14]. The underlying mechanisms are believed to include not only caloric restriction but also hormonal changes that enhance insulin sensitivity and pancreatic β-cell function, modulation of bile acid metabolism, increased release of incretins like GLP-1, and suppression of appetite-regulating hormones such as ghrelin [15].

Our study reinforces earlier findings that obesity is associated with elevated levels of inflammatory molecules, such as interleukins (IL-1β, IL-6, IL-8, IL-10) and tumor necrosis factor alpha (TNF-α), which collectively contribute to systemic inflammation and insulin resistance [16–20]. In line with other reports, we observed significant reductions in proinflammatory markers, including IL-1β, IL-12, IL-23, and CRP, within six months of SG. These changes suggest a beneficial shift in the immune environment following surgical weight loss, which may explain the improvements in metabolic outcomes often seen in bariatric patients [21,22].

Cytokines are key signaling proteins in the immune system, and their levels can respond to changes in body composition, nutrient intake, and hormonal balance. While the precise roles of many cytokines remain incompletely understood, our results provide strong evidence that bariatric surgery reduces systemic inflammation. Importantly, we found that the extent of weight loss was associated with greater reductions in inflammatory markers, indicating a dose-response effect. This highlights the potential of SG not only as a weight-loss tool but also as a strategy to mitigate obesity-induced immune dysfunction.

Although our study supports the anti-inflammatory and metabolic benefits of SG, it also addresses a research gap specific to Iraq, where limited data exists on the immunological outcomes of bariatric surgery. These findings contribute valuable local insights and underscore the relevance of SG as a therapeutic option in a region experiencing a growing burden of obesity.

Strengths of the Study

This study offers several notable strengths. First, it evaluated a broad panel of inflammatory markers, including IL-1β, IL-12, IL-23, IL-33, IFN-α, IFN-γ, and MCP-1, providing a comprehensive view of immune system changes following sleeve gastrectomy. Second, patients were assessed at two postoperative intervals three and six months which enabled the tracking of short-term trends and the stability of changes over time. Finally, the study adds region-specific insight by focusing on an Iraqi population, where obesity is a growing concern and local data on bariatric outcomes remain limited. This contributes new evidence that may help inform treatment strategies within similar healthcare contexts.

Limitations of the study

This study has several limitations that should be acknowledged. The relatively small sample size of 40 patients may limit the statistical power and generalizability of the results. Conducted at a single private clinic in Baghdad, the findings may not reflect broader or more diverse populations. The absence of a non-surgical control group restricts the ability to attribute observed changes solely to sleeve gastrectomy, as other lifestyle or medical factors could have influenced outcomes. Additionally, the follow-up period of six months provides only short-term insights, and long-term effects on inflammation and metabolic health remain unknown. The reliance on self-reported adherence to diet and lifestyle modifications may also introduce bias and affect the interpretation of metabolic improvements. Future studies with larger, multicenter cohorts and longer follow-up are recommended to validate and expand upon these findings.

Implications for Clinical Practice

The results suggest that sleeve gastrectomy should be considered not only for weight reduction but also for its anti-inflammatory benefits. Clinicians may use inflammatory markers such as CRP or IL-1β to monitor postoperative recovery and gauge the success of metabolic improvements. Furthermore, discussing the immune and metabolic benefits of the surgery with patients may improve decision-making and encourage uptake, particularly among those hesitant about surgical options. This research supports incorporating immune health into post-surgical evaluations.

This study demonstrates that sleeve gastrectomy leads to significant weight loss and a marked reduction in systemic inflammation within six months post-surgery. The observed decreases in key inflammatory cytokines, such as IL-1β, IL-12, and IL-23, suggest an improvement in immune balance that may contribute to better metabolic health. These findings highlight the dual benefit of bariatric surgery not only as an effective intervention for obesity but also as a potential modulator of chronic inflammation. The results support the use of sleeve gastrectomy as a therapeutic option for improving both physical and inflammatory profiles in obese patients, particularly within the Iraqi healthcare context.

Future Recommendations

To build on these findings, future research should include a larger, more diverse sample and be conducted across multiple centers in Iraq or other regions. Including a non-surgical control group would also strengthen causal inferences. Long-term follow-up beyond six months is recommended to assess the durability of the observed improvements in inflammation and metabolic function. Additionally, future studies could investigate the psychological and quality-of-life outcomes associated with cytokine reduction and improved immune function after bariatric surgery.

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