The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

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The biodistribution of radioactivity after the administration of a new tracer for alpha4beta2 nicotinic acetylcholine receptors (nAChRs), [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), was studied in ten healthy human subjects. Following administration of 98+/-6 MBq [123I]5-I-A-85380, serial whole-body images were acquired over 24 h and corrected for attenuation. One to four brain single-photon emission tomography (SPET) images were also acquired between 2.5 and 24 h. Estimates of radiation absorbed dose were calculated using MIRDOSE 3.1 with a dynamic bladder model and a dynamic gastrointestinal tract model. The estimates of the highest absorbed dose (microGy/MBq) were for the urinary bladder wall (71 and 140), lower large intestine wall (70 and 72), and upper large intestine wall (63 and 64), with 2.4-h and 4.8-h urine voiding intervals, respectively. The whole brain activity at the time of the initial whole-body imaging at 14 min was 5.0% of the injected dose. Consistent with the known distribution of alpha4beta2 nAChRs, SPET images showed the highest activity in the thalamus. These results suggest that [123I]5-I-A-85380 is a promising SPET agent to image alpha4beta2 nAChRs in humans, with acceptable dosimetry and high brain uptake.

The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33 +/- 15 years) participated in both a bolus (dose: 317 +/- 42 MBq) and a bolus plus constant infusion (dose of bolus: 98 +/- 32 MBq, B/I=6.7 +/- 2.6 h, total dose: 331 +/- 55 MBq) study. The study duration was 5-8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (VT') and specific (VS') distribution volumes. A two-tissue compartment model was applied to identify VS'. VT' was also calculated in B/I studies. In bolus studies, VT' was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave VT' values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm(-3) in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify VS' well. B/I studies provided poor accuracy of VT' measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [123I]5-I-A-85380 in humans and support the use of VT' measured by bolus studies.