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Figure 4. (A and B) Treg/IL-2 combination therapy suppressed CCL2 and IL-18 levels with a concomitant increase in both when not on Treg therapy but still receiving IL-2 in two of three phase I subjects. During the six-month Treg “washout” period, when subjects were receiving only IL-2, CCL2 and IL-18 levels rose towards the baseline level with a coinciding deterioration of the AALS. With a second round of infusions, administered every four weeks for a total of 4 infusions, the therapy suppressed CCL2 and IL-18 levels and the subjects’ clinical statuses stabilized. At the end of the study when Treg infusions ceased and only IL-2 was continued, CCL2 and IL-18 levels gradually increased again. The stabilization and deterioration of the subjects’ clinical statuses mirrored the decline and rise of serum CCL2 and IL-18 levels; (C) The third subject had increased levels of CCL2 that was refractory to Treg/IL-2 therapy; IL-18 was not elevated in subject 3 throughout the study. However, similarly to the other two subjects, subject three’s progression stabilized when receiving Treg/IL-2 therapy but progressed again when Treg therapy was stopped and only IL-2 was administered. Arrows indicate Treg infusion dates. The red dotted lines demarcate Treg + IL-2 therapy or IL-2 only intervals. Red line = mean value of each analyte in HC. Black lines ± one standard deviation of each analyte level in HC. The means and standard deviations vary due to the differences in ELISA plates used. AALS: Appel ALS clinical scoring system.