As a consequence, the distribution of IgM expressed by the AUC of serum IgM over time was significantly greater for survivors than for non-survivors. This finding was similar both when outcome was assessed after 28 days and at hospital discharge (Figure 4A and and44B).Figure 4Kinetics of immunoglobulin M (IgM) upon progression to shock. Thirty patients with severe sepsis progressed Abiraterone Sigma into septic shock. Serum IgM was measured immediately after start of vasopressors (day 0) until day 6. Results are presented separately for survivors …Production of IgM by PBMCs of 55 patients was also studied. From these patients, 24 had uncomplicated sepsis, 20 severe sepsis and 21 septic shock. Respective mean �� SD age was 66.5 �� 18.7, 76.4 �� 9.2 and 60.0 �� 21.4 years; mean �� SD APACHE II score was 10.

7 �� 5.4, 17.4 �� 4.3 and 23.6 �� 4.8; and mean �� SD white blood cell count was 12,226.4 �� 5,262.0, 16,384.0 �� 11,294.0 and 17,130.9 �� 9,793.7/mm3.High production of both IgM and TNF�� was found by the PBMCs of healthy volunteers after stimulation with the selective lymphocyte agonist PHA. Production of IgM and of TNF�� was significantly lower at all stages of sepsis compared with healthy controls (Figure 5A and and5B).5B). Furthermore, the rate of ‘IgM producers�� was significantly lower among patients with septic shock than among patients at all other sepsis stages (Figure 5C).Figure 5Production of immunoglobulin M (IgM) by mononuclear cells. Peripheral blood mononuclear cells (PBMCs) were isolated from 21 healthy volunteers, 24 patients with sepsis, 20 patients with severe sepsis and 11 patients with septic shock.

PBMCs were stimulated …DiscussionThe present study is the largest cohort to the best of our knowledge that describes the kinetics of circulating IgM in sepsis. Analysis indicates that the decrease of IgM is a predominant characteristic when a patient with severe sepsis develops septic shock. Close monitoring from the start of vasopressors shows that the distribution of IgM is greater in survivors than in non-survivors from septic shock.These conclusions are based on the multilevel approach of the current study; at first, comparisons between SIRS, sepsis, severe sepsis and septic shock indicated that septic shock is the stage of critical illness with the lower circulating IgM; then measurements at distinct time points that is, upon initial diagnosis and upon worsening showed that circulating IgM decreases specifically upon progression from severe sepsis to septic shock; and finally, intense monitoring of IgM after the start of vasopressors revealed a relationship between lacking distribution of IgM and unfavorable prognosis.

IgM levels in patients with septic shock are reported in two more studies. In the first study [14], IgM was decreased in 21 patients with septic Cilengitide shock.